Patients with ulcerative colitis (UC) limited to distal segments of the colon and rectum are often poorly represented in large clinical therapeutic trials, yet they constitute up to two-thirds of all UC patients. The propensity of UC to be most severe distally has also resulted in many oral or systemic therapies with lower levels of therapeutic success and mucosal healing in the distal regions of the colon. Topically administered mesalamine and corticosteroid agents have been utilized for decades in patients with distal UC but are often poorly accepted by patients and their prescribing physicians due to difficulties in administration and embarrassment. Formulation advances in the mesalamine preparations have led to the addition of topical 5-aminosalicylic acid (5-ASA) foams and gels to the existing options of liquid enemas and suppositories. Comparable advances in the use of topical corticosteroids have also taken advantage of the development of topical budesonide and similar safer corticosteroid preparations that promise clinical efficacy while delivering fewer systemic corticosteroid side effects. Combination therapy with oral and topical 5-ASA agents, or with topical 5-ASA and topical corticosteroid compounds, has further expanded the armamentarium for prescribers. Novel topical applications of currently existing therapies such as tacrolimus and cyclosporine show varying degrees of promise; the growing area of biologic and novel small molecules raises the possibility of a new wave of topically applied therapies for patients with distal UC and ulcerative proctitis.