Cutaneous leishmaniasis is a major tropical infection caused by vector-borne protozoa of the Leishmania species. Disease presentation, clinical course, prognosis and response to therapy is species- and geographic region-dependent. A wide variety of treatment modalities exist for the diverse spectrum of clinical disease. Traditional antileishmanial systemic agents such as antimonials, pentamidine and amphotericin are limited by toxic side effects, parenteral route of administration and emerging drug resistance. Newer agents such as oral miltefosine have shown efficacy and tolerability. However, use of systemic pharmacotherapies remains limited by their relative high cost in developing countries and despite advances in basic scientific research, there has been little progress in new drug development for what remains a neglected disease afflicting 12 million of the world's poorest population. This article examines the merits of existing and emerging therapies and reasons for variation in therapy response.