For years, NIH enjoyed a growing budget and a responsive medical-research community that increased its ranks and its grant applications accordingly. These days, with deficit reduction on the minds of policymakers and the sequester cuts in effect, those numbers are trending in a different direction. That makes the job facing Collins, 63, the nation's foremost grant-giver, more difficult than ever, as the money he has to support basic science research has declined for the first time in decades. "It makes it very hard," he says. "And this is the paradox of my current existence, to be in a position of seeing science developing at the greatest pace I've ever seen, but seeing the funding for science never under greater threat." Nearly every government function is facing cuts now, but because of NIH's grant-making mission and its long-term investments, Collins says, the current reductions are tougher for his agency to absorb. His job will be to advocate for more research dollars—and make the most of limited resources if he's unsuccessful. A trained physician (M.D. from the University of North Carolina) and medical researcher (Yale physical chemistry Ph.D.), Collins ran the Human Genome Project, learning how ambitious scientific undertakings can generate collaboration and important results. He has launched a similar initiative to map the human brain. Collins earns plaudits from Congress for his breezy explanation of complex science—an important skill in selling research that typically takes years to translate into bedside treatments. The Virginia native is also a character, performing in a classic-rock-style band sometimes called The Directors and riding his Harley Davidson motorcycle on the weekends. Collins maintains his own small research lab, where he studies diabetes. But his job these days is mostly managerial. The question that keeps him up at night: "How are we going to manage our budget when it just took a $1.5 billion cut?"