Objective.To report a patient with a rare clinical presentation of marginal keratitis and pyoderma gangrenosum (PG) that responded to the steroid-sparing agent azathioprine.Design.Interventional case report.Methods.Case report and MEDLINE review of the medical literature on PG-associated peripheral ulcerative keratitis (PUK) and its treatment.Results.A patient with a biopsy-proven history of PG developed an explosive episode of PUK. The ocular inflammation was minimally responsive to topical therapy and required significant long-term oral steroids for control. The patient's active skin lesions and marginal keratitis responded dramatically to systemic oral azathioprine. Since the initiation of treatment with azathioprine, there have been no subsequent recurrences of PG or marginal keratitis.Conclusions.PUK may be associated with other inflammatory conditions, such as PG and arthritis. Systemic azathioprine may successfully control ocular and extraocular conditions and should be considered in the clinical setting of topical therapy failure and/or extraocular inflammatory conditions.