Evidence of ocular immune privilege was noted almost 130 years ago. The past 30 years have witnessed an explosion in research on ocular immune privilege. One of the primary mechanisms that contribute to ocular immune privilege is the unique form of immune deviation that is invoked when antigens are introduced into the anterior chamber (AC) of the eye - a phenomenon termed AC-associated immune deviation (ACAID). ACAID embodies a constellation of cellular interactions and at least four different organ systems: eye, thymus, spleen, and sympathetic nervous system. At least four different cell populations interact to generate CD8+ T regulatory cells that suppress both Th1- and Th2-mediated inflammation. The interactions that occur between F4/80+ antigen-presenting cells, CD4+ T regulatory cells, NK1.1+ T cells, γδ T cells, B cells, and CD8+ T cells remain to be fully elucidated. Ocular immune privilege was originally perceived as a simple anatomic anomaly that has evolved to be one of the most sophisticated and intriguing forms of immune regulation.