The queen of media is embracing the milestone, as are her celebrity friends.
Her talk show is seen in 141 countries. Two million fans read her magazine each month. She can turn an unknown book into a best-seller. She's truly a global celebrity. And when she has a birthday, everyone knows about it.
Early Show national correspondent Hattie Kauffman took a closer look at the many facets of Winfrey and how she celebrates her birthday in style.
"No expense was spared in her 50th birthday party. It was a black-and-white-themed party at her ranch in Montecito, California. A-list celebrities were there, evryone you can imagine," said Ashley Dillahunty, bureau chief of In Touch Weekly.
In the last decade, Oprah has been giving back. She opened a girls' school in South Africa and launched her Angel Network, which has given $80 million to charity.
"So what kind of birthday present do you give a woman who has everything?" Kauffman asked.
"I know what I'd get her. I'm going to give her a donation to her school in Africa," said her longtime friend, actress Jennifer Aniston.
"A big, fat kiss. And I love you," said comedian and "30 Rock" star Tracy Morgan.
"Obama's president. What more do you get someone?" remarked actor John Slattery, knowing Winfrey is a die-hard Obama supporter.
She already qualifies for an AARP card, but Winfrey shows no sign of wanting to retire.
"I think the older she gets, the more successful she gets, and the more ideas come to her, and she just is building and building her empire. So Oprah will never stop working," Dillahunty said.
"Besides, if she retired, who would we turn to for advice on everything from books to bras?" Kaufmann kidded.
Winfrey even got Screen Actors Guild Life Achievement Award-winner James Earl Jones to sing "Happy Birthday" in his amazing voice, resonating a genuine love for the talk show host who still surprises us all.