Sine oculis (so) and eyes absent (eya) are required for Drosophila eye development and are founding members of the mammalian Six and Eya gene families. These genes have been proposed to act with eyeless (Pax6) to regulate eye development in vertebrates and invertebrates. so encodes a highly diverged homeobox transcription factor and eya encodes a novel nuclear protein. We demonstrate that So and Eya (1) regulate common steps in eye development including cell proliferation, patterning, and neuronal development; (2) synergize in inducing ectopic eyes; and (3) interact in yeast and in vitro through evolutionarily conserved domains. We propose that an So/Eya complex regulates multiple steps in eye development and functions within the context of a network of genes to specify eye tissue identity.