Many crucial cellular enzymes--including RNA polymerases, kinases, phosphatases, proteases, acetylaters, etc.--have multiple potential substrates. Regulation entails substrate selection, a process effected by a mechanism we call regulated localization. This formulation is particularly well illustrated by the mechanisms of gene regulation. Analysis of these mechanisms reveals that regulated localization requires simple molecular interactions. These molecular interactions readily lend themselves to combinatorial control. This system of regulation is highly 'evolvable'. Its use accounts, at least in part, for the nature of many of the complexities observed in biological systems.