Iris nodules are an uncommon clinical sign in uveitis. The diseases most commonly associated with iris nodules and uveitis include sarcoidosis, Vogt-Koyanagi-Harada syndrome, multiple sclerosis, Fuchs' heterochromic iridocyclitis, and metastatic infection. While many of these diseases may be appropriately treated with immunosuppressive medication, the management of infectious uveitis is antimicrobial therapy. Inappropriate immunosuppressive therapy may result in a poor outcome for the patient with an infection. Consequently, cases of uveitis with iris nodules were reviewed to identify clinical features that may help differentiate infection from non-infectious inflammation.The clinical database of 1353 consecutive patients evaluated at a tertiary care referral based North American uveitis clinic were retrospectively reviewed to identify cases of infectious uveitis with iris nodules. A Medline search was performed to identify additional cases. From these cases information regarding clinical presentation, diagnosis, treatment, and outcome were collected.Three cases (three eyes) were identified from the authors' own records of infectious uveitis with iris nodules. An additional 25 cases of infectious uveitis with iris nodules were identified in 22 published reports. Analysis of the authors' cases and these reports showed that infectious uveitis with iris nodules was specifically characterised by some or all of the following: (1) creamy, soft appearance to the nodule(s), (2) unilateral disease, (3) persistence or growth of the nodule(s) despite corticosteroid therapy, (4) marked inflammatory response in the anterior chamber and/or vitreous humour, and/or (5) history suggesting a potential source of septic emboli.Certain features of the clinical history and examination are useful in the diagnosis of metastatic infection in patients presenting with uveitis and iris nodules.