Biochemistry and structural biology are undergoing a dramatic revolution. Until now, we have tried to study subtle and complex biological processes by crude in vitro techniques, looking at average behaviors of vast numbers of molecules under conditions usually remote from those existing in the cell. Researchers have realized the limitations of this approach, but none other has been available. Now, we can not only observe the nuances of the behaviors of individual molecules but prod and probe them as well. Perhaps most important is the emerging ability to carry out such observations and manipulations within the living cell. The long-awaited leap to an in vivo biochemistry is at last underway.