Cells modulate their metabolism, growth and proliferation in response to external stimulii. We use advanced fluorescence microscopy methods to characterize, in live cells, the proteins implicated in environmental regulation of cellular expression programs and cell state transitions. The approaches we use include scanning fluctuation microscopy, fluorescence lifetime imaging/phasor and single molecule localizaiton super-resolution microscopy. With these tools we have investigated the the role of biological noise in the transcriptional switch between glycolysis and gluconeogenesis in B. subtilis, regulation of the balance between growth and division in budding yeast and its control by nutrients, the molecular basis for the pressure-induced SOS response in E. coli and the stoichiometry of postsynaptic density complexes and glutamate receptors in live neurons. In each case our studies revealed fundamental molecular mechanisms responsible for the regulation of important biological functions.