To investigate the molecular mechanisms of development, it is useful to be able to turn genes both on and off in a spatially restricted manner. Although the development of photo-activated morpholino oligonucleotides (photo-MOs) has made it possible to turn genes off at specific times and places, finding a way to deactivate MOs and restart gene expression has proved more elusive. Here (p.1691), Alexandra Tallafuss, Philip Washbourne and colleagues describe an approach in which they can turn genes off and on using sense photo-MOs (S-photo-MOs) and complementary antisense photo-MOs (AS-photo-MOs), respectively. S-photo-MOs bind to and block the activity of regular morpholinos, and exposure of the S-photo-MOs to UV light allows the morpholinos to become active and block gene expression; AS-photo-MOs block gene function like regular morpholinos, but normal gene function can be restored by light inactivation. Importantly, the researchers demonstrate the feasibility of their new approach in whole zebrafish embryos by studying notochord induction and neural crest development, and in single cells by temporally manipulating Gal4 transgene expression.