Topic To provide recommendations for the use of anti-tumor necrosis factor α (TNF-α) biologic agents in patients with ocular inflammatory disorders. Clinical Relevance Ocular inflammatory diseases remain a leading cause of vision loss worldwide. Anti-TNF-α agents are used widely in treatment of rheumatologic diseases. A committee of the American Uveitis Society performed a systematic review of literature to generate guidelines for use of these agents in ocular inflammatory conditions. Methods A systematic review of published studies was performed. Recommendations were generated using the Grading of Recommendations Assessment, Development, and Evaluation group criteria. Results Numerous studies including controlled clinical trials have demonstrated that anti-TNF-α biologic agents (in particular infliximab and adalimumab) are effective in the treatment of severe ocular inflammatory disease. Based on these studies, the expert panel makes the following recommendations. Conclusions Infliximab and adalimumab can be considered as first-line immunomodulatory agents for the treatment of ocular manifestations of Behçet's disease. Infliximab and adalimumab can be considered as second-line immunomodulatory agents for the treatment of uveitis associated with juvenile arthritis. Infliximab and adalimumab can be considered as potential second-line immunomodulatory agents for the treatment of severe ocular inflammatory conditions including posterior uveitis, panuveitis, severe uveitis associated with seronegative spondyloarthropathy, and scleritis in patients requiring immunomodulation in patients who have failed or who are not candidates for antimetabolite or calcineurin inhibitor immunomodulation. Infliximab and adalimumab can be considered in these patients in preference to etanercept, which seems to be associated with lower rates of treatment success. © 2014 by the American Academy of Ophthalmology.