Last year, he made his directing debut with a new movie, "Confessions of a Dangerous Mind," which will be re-released this weekend and on home video this fall.
When 60 Minutes first aired this story in January, Clooney was basking in some pretty good reviews. Personally and professionally, it seems everyone who meets George Clooney succumbs to his charms. Correspondent Dan Rather reports.
On this day, Clooney's appeal is completely lost on his sleeping 200-pound pig Max.
"Normally, he sleeps at the end of my bed, but now he's gotten so fat," says Clooney, who admits that Max doesn't help with the ladies, but "he's my longest relationship."
Clooney may not be known for long relationships with women, but it's certainly not for lack of opportunity. It is Clooney's blessing and curse to be a heartthrob. Even his best movies are built around his looks.
If Clooney takes all this in stride, it's because he understands show business in a way most beginners don't. He grew up watching his aunt Rosemary Clooney, a singer and actress who appeared in classic films like "White Christmas."
"When she was 21, 22 years old, she was the biggest thing on the cover of Life magazine, and singing and everybody loved her," he says.
"She went out on the road. And while she's on the road, rock 'n' roll comes around and all women singers are gone. And suddenly, they start telling her how bad she is in what she did. So she went through a very bad period of time, of hating herself, drugs, you know lost all of her money. So, by example, she was a great lesson to me about how to deal with fame, which there is no handbook for."
Her story has become a cautionary tale for her nephew: "You have to have control. Because if you leave it up to other people, at the end of the day, it will fall apart. And I would rather, when it falls apart, it be in my hands and not in someone else's."
That's why he has moved into directing. His first film, "Confessions of a Dangerous Mind," is a complicated, dark comedy based on the life of TV game show king Chuck Barris, who created The Dating Game, The Newlywed Game, and The Gong Show.
"This was a great script and I wanted it to get made," says Clooney. "And it seemed the only way that it was gonna get made was if I sort of picked it up and shoved it over the wall. So I did it. But directing scared me."
The movie focuses on Barris' wild claim that he led a secret life as a CIA assassin while making millions in game shows.
The story had knocked around Hollywood for a few years, but it took Clooney's clout to get it made - in part because he could enlist the help of friends like Drew Barrymore and Julia Roberts.
To prepare for making the movie, he pored over tapes of Barris' game shows. And 60 Minutes II watched the Old Gong Show with Clooney, who revels in its shamelessness.
When The Gong Show began in 1976, it was denounced as the worst program ever to hit the airwaves. In retrospect, it's simply silly - a talent show for those with little talent, where contestants either won worthless prizes, or got the gong.
Barris was the hapless master of ceremonies. "What the film's about was a man going through a period of really hating himself and feeling like he woke up one day and wasn't any of the things he thought he was, any of the things he thought he was going to be," says Clooney.
The world of game shows is familiar ground for Clooney. His father, Nick Clooney, had a long broadcasting career and once hosted a network TV game show called "The Money Maze."
"There was a big maze and the husband would run through and the wife would stand above it and go 'Go left, Go right,'" says Clooney. "And there was a real innocence to it, it was really fun. So I wanted to capture that again."
For Clooney, "Confessions of a Dangerous Mind" is about the loss of that innocence, about what happens when one man realizes his life and his work haven't added up to much.
"We all have those fears of not counting somehow, not really mattering, not making a difference one way or another," says Clooney. "I've been part of really bad television shows. I know what that's like. I've been in really bad films and I know what that feels like. So you spend a lot of time making up for that or trying to make up for that."
We may remember Clooney best for his role as a womanizing doctor on "ER," or for his work on films like "Ocean's Eleven," "Three Kings," or "O, Brother, Where Art Thou?"
But Clooney can't forget his more spectacular failures. "I've done a few bad ones. It's tough. I'm in one of the more celebrated bad films called 'Return of the Killer Tomatoes.' I say lines like 'That's the bravest thing I've ever seen a tomato do' with a straight face. That's a bad film," he says with a laugh.
Clooney loves to laugh at himself and others. He has a reputation as a world-class practical joker who's left a long trail of victims. And he has laughed all the way to the bank.
He has a beautiful home in Hollywood that stretches over several secluded acres, with its own tennis court, screening room, guest house, swimming pool, and antique motorcycles. There's plenty to keep Clooney busy. It is the kind of life most Americans can only dream about.
He lives there alone, except for his pig and two bulldogs. But he says his close circle of friends and his family keep him sane - and that he still has a Midwestern sensibility to a certain extent.
What about his social life? Do women constantly call him? "It's not quite I think what people think. When you are in the position I'm in there are women that approach you all the time. People in general approach you. But they have no personal connection to you," says Clooney.
"That's very interesting for the first six months of being famous when a bunch of girls show up, and then, it becomes embarrassing. It's embarrassing. It's embarrassing to walk in a place and have somebody make a scene about you. You can't help but be embarrassed if you have any sort of modicum of decency. You're embarrassed by it."
But it's hard to feel too sorry for him, particularly now. With good reviews for his movie, there is a recognition that Clooney has become a creative force.
"You go from just being the guy getting the job, to those jobs happening because you're doing them. And slowly you come to the realization that you have a responsibility with those jobs, to keep the bar high, to raise the bar."
Clooney is one of life's lottery winners - a man with both good luck and good looks. But will it last?
He's leaving little to chance: "It happens to everyone. Things change. The world changes. So I understand it. I'll go kicking and screaming, but I understand it. That's why you direct and why you produce and why you write - to try and create these other avenues that you can keep alive because you can't stay in front of the camera all that long."