A pioneer in single-molecule live-cell research, Professor Sunney Xie was chosen as one of nine winners of the inaugural NIH Director’s Pioneer Award in 2004. In 2006 Xie’s group at Harvard University was the first to record real-time movies of protein production one molecule at a time in bacteria, a breakthrough that enabled quantitative description of gene expression. He continues to pursue exploratory work with the potential of high return—and the inevitable high risk.