The discovery of the association of HLA B27 with spondyloarthropathy led to more questions than answers about the role of this gene in disease susceptibility. The realization that HLA B27 was not responsible for all of the genetic effects helped to lay a foundation for further investigation into the genetics of uveitis. Over several decades, genetic findings have provided clues to advance the understanding of mechanisms of uveitis and to catalyze new research on diagnostics, animal models, and therapies. From the early candidate gene studies on immune mediators to the recent genome-wide investigations, much has been discovered. However, these discoveries have come with the caveat that a genetic finding does not automatically reveal the disease-relevant functional effect of the associated variant.