The overall goal of this review is to highlight the power of zebrafish as a model system for studying complex diseases which involve multiple genetic loci. We are interested in identifying and characterizing genes implicated in the blinding condition of glaucoma. Glaucoma is a complex disease that often involves multiple genetic loci. Most disease causing and modifying genes for glaucoma remain unidentified. However, several genes that regulate various aspects of ocular development have been shown to associate with glaucoma. With zebrafish, forward and reverse genetic approaches can be combined in order to identify critical genetic interactions required for normal and pathological events in the development and maintenance of the eye.