Not only does he have two hit albums and a Grammy Award, but he is also starting a new line of clothing named Applebottoms. But all his success has been overshadowed by his half-sister's continuing fight with leukemia.
The Early Show co-anchor Rene Syler spoke with the rapper about his efforts to help her get well.
The St. Louis native struck hip hop gold when his first two CDs went multi-platinum. But a dark cloud entered Nelly's life when his half-sister, Jackie Donahue, was diagnosed with leukemia.
"You definitely think the worst when you hear stuff like that," says Nelly, "Because, you know, I'm ignorant to the fact of leukemia."
But, he received a quick education on the disease.
"I just try to be there for her and just to let her know that there's people who made it through this, there are people who are making it through this, and [she's] going to be one of those persons who makes it through also," Nelly says.
But Donahue's situation took a turn for the worse when she learned that her chemotherapy wasn't working and she would need a bone marrow transplant.
"The doctor said, 'Well, look, there's nothing else we can do right now. But the best thing to do is maybe a bone marrow transplant. And there's not many African Americans on the registry,'" recalls Donahue. "It's not only me that needs a bone marrow transplant. But it's other African Americans that need one also.
"I'm just imagining how they're feeling. You know, they may not have a lot of support like I have at this time. And I felt real bad. Like, what are we supposed to do?"
Fortunately, someone did know what to do. Nelly organized a bone marrow donor registration drive when he heard Donahue needed a bone marrow transplant.
He also got his celebrity friends to appear in a public service announcement to encourage people to register.
Nelly says he wants people to know about the bone marrow registry and sign up for it.
"It can happen to you. This can happen in your own backyard. This can happen in your own bed. This could be your spouse lying next to you. This could be your child in the next room," he explains. "You never know until you get the papers back, or till you get the tests back or whatever the case is."
The rapper believes a donor will be found for Donahue.
"I have to dwell on the positive and keep moving," he says. "And to keep [Donahue] positive about the situation. When you think positive, positive things happen. That's just been the whole philosophy of my life ... And this is no different. So I'm sure we're going to find one."
Donahue shares her brother's faith that a marrow donor match will be found, and she says Nelly's support has made a world of difference.
"You know you'll always have that brotherly love, that brother support, that sister support," she says. "But when something like this happen, that really let me know that no matter what happens, I always have his support — regardless what it is. So I wasn't surprised and I wasn't shocked. But that's the type of person that he is."
So, after all Nelly's success, his hits and his Grammy, he says he won't be completely happy until his sister is well again.
"I try not to get down, but I do," says Nelly. "If I do, it's basically on myself because I feel I can do more or I feel I can do better."
Nelly says he hasn't done enough because his family hasn't found a donor for his sister.
"I just feel like this is what any brother would do for their sister," he says. "That's what family does. So you try to stick by that."