Sphingolipids are essential to cell membrane structure and the development and maintenance of neural tissues. The role of bioactive sphingolipids has been established in numerous cellular events, including cell survival, growth, and apoptosis. Ocular inflammatory and autoimmune diseases involve activation and migration of endothelial cells, neovascularization, and infiltration of immune cells into various tissues. Clinically, the impact and role of sphingolipid-mediated signaling is increasingly being appreciated in the pathogenesis and treatment of diseases ranging from multiple sclerosis to neovascularization in age-related macular degeneration and diabetic retinopathy. In this review, we discuss our current knowledge and understanding of sphingolipid metabolism and signaling associated with the pathogenesis of ocular diseases.