Display omitted •Insert domains to allosterically control the active site with light or rapamycin.•Computational approach finds surface loops allosterically coupled to active site.•Generate split proteins with reduced spontaneous assembly.•Algorithm to assist finding sites to generate split proteins.•Tested on GTPases, GEFs and kinases. Optogenetics, genetically encoded engineering of proteins to respond to light, has enabled precise control of the timing and localization of protein activity in live cells and for specific cell types in animals. Light-sensitive ion channels have become well established tools in neurobiology, and a host of new methods have recently enabled the control of other diverse protein structures as well. This review focuses on approaches to switch proteins between physiologically relevant, naturally occurring conformations using light, accomplished by incorporating light-responsive engineered domains that sterically and allosterically control the active site.