Uveitis, or inflammation of the uveal tract (i.e., iris, ciliary body, and choroid), results from a heterogeneous collection of disorders of varying etiologies and pathogenic mechanisms. Uveitis is caused by a systemic disease in 30% to 45% of patients. Primary care physicians may be asked to evaluate patients with uveitis when an underlying systemic diagnosis is suspected but not apparent from eye examination or history. If the history, physical examination, and basic laboratory studies do not suggest an underlying cause, serologic tests for syphilis and chest radiography for sarcoidosis and tuberculosis are recommended. Typing for human leukocyte antigen-B27 is appropriate for patients with recurrent anterior uveitis. Because the prevalence of many rheumatologic and infectious diseases is low among persons with uveitis, Lyme serology, antinuclear antibody tests, serum angiotensin-converting enzyme tests, serum lysozyme tests, and tuberculin skin tests can result in false-positive results and are not routinely recommended. Drug-induced uveitis is rare and can occur from days to months after the time of initial exposure. Primary ocular lymphoma should be considered in persons older than 50 years with persistent intermediate or posterior uveitis that does not respond to anti-inflammatory therapy.