Scleritis and peripheral ulcerative keratitis (PUK) can present as isolated conditions or as part of a systemic inflammatory or infectious disorder. Both are serious ocular conditions that can result in vision loss and require early diagnosis and treatment. Nearly two thirds of patients with non-infectious scleritis require systemic glucocorticoid therapy and one fourth need a glucocorticoid-sparing agent as well. Essentially all patients with non-infectious PUK require systemic glucocorticoids. A detailed clinical history, thorough physical examination, and thoughtful laboratory evaluations are important in the exclusion of underlying disorders and extraocular involvement.