Phenotypic traits constitute the interface between the organism and the environment. Adaptive evolution occurs when trait responses to the environment maximize fitness subject to constraints. These constraints can be morphological, biochemical or genetic. On the one hand, evidence of rapid evolution in response to environmental perturbations (e.g., pollution, habitat degradation, climate warming) suggests that evolution in response to these novel selection pressures can proceed unconstrained. On the other hand, evidence of extinctions and disruptions of species interactions suggests that constraints can impede evolution in response to novel selective regimes. There is much we do not understand about the interplay between selection and constraints, particularly in light of anthropogenically-induced selection regimes. I am particularly interested in the role of biochemical constraints in reaction norm evolution. This interest is fueled by my work on temperature effects on ectotherm life history, population dynamics and species interactions. I want to gain a mechanistic understanding of biochemical constraints all the way from protein folding to enzyme kinetics so that I can incorporate these mechanisms into models of reaction norm evolution. There is a great deal I do not understand about these processes themselves and how they translate into the mathematics of population dynamics. I do, however, entertain some speculations about the role of how biochemical constraints in irreversible outcomes in phenotypic evolution.