We reviewed our experience in the management of 47 patients (61 eyes) with peripheral ulcerative keratitis (PUK) to establish guidelines for appropriate indications to consider institution of systemic chemotherapy. Fifty-three percent of patients had a systemic disease as the etiology of PUK; one fourth of these were newly diagnosed as a result of meticulous history taking. The histologic demonstration of vasculitis in ocular tissue was the crucial step in deciding on chemotherapy in more than half of our patients. The presence of scleritis was highly associated with active vasculitis. Twelve of 14 patients with bilateral PUK required chemotherapy. Recommendations for an approach to therapy of PUK are presented.