From subcellular molecular networks to ecological communities, how living systems respond to external stimuli is a core aspect of biological function.  Here, theoretical modeling built on physical principles can help us understand the underlying mechanisms.  In this talk, I discuss two such examples.  The first is a nonequilibrium limit to how sensitively a biochemical system can respond to an external perturbation.  To illustrate this result, I will draw on examples from biophysics, where the effectiveness of numerous biochemical systems depends on being exquisitely sensitive to changes in chemical inputs.  We will see how these predictions rationalize known energetic requirements of some common biochemical motifs and provide new limits to others.  The second is a study of how cooperativity and spatial structure in bacterial biofilms conspire to lead to a community-level antibiotic resistance.  I will present experiments measuring the population dynamics of coupled spatially fixed biofilms and planktonic populations of a mixture of drug-sensitive and resistant E. faecalis.  Matched with theoretical modeling, we surprisingly find no spatial structure in the biofilm even though there is a common population inversion, in which the final fraction of resistant cells exceeds its initial value, particularly at smaller initial resistant fractions.