How does a network of interacting proteins work to accomplish a complex cellular function with extreme temporal and spatial precision? The accumulation of a large body of knowledge over the last 50 years has paved the way to understanding the biology of the cell in amazing detail. While many molecules have been discovered, their effects mapped by genetics and mutational analysis, and in some cases their three dimensional structures solved with x-ray crystallography and EM, we still do not fully understand the physical basis of many cellular events. I believe that by watching the functional behavior of these large meso-scale complexes in living cells—the native states of the enzymes—we will more clearly understand their complexity, regulation, and mechanisms.