In the post-genomic era, a central challenge of modern biology and medicine is the need to understand how the interactions of protein machines affect the physiology and the pathology of cells and tissues. Optical imaging and spectroscopy afford unprecedented opportunities in studying these dynamical processes in vivo. In this lecture, I will focus on two microscopy technologies. First, high through-put tissue cytometry allows the molecular origins of carcinogenesis and muscular diseases to be investigated on the organ level. Second, lifetime-resolved fluorescence resonance energy transfer is applied to study protein interactions that regulate cellular mechanotransduction processes.