The diagnosis of leishmaniasis can be challenging because it mimics both infectious and malignant conditions. A misdiagnosis may lead to an unfavorable outcome. Using culture, histologic, and/or polymerase chain reaction study results, a diagnosis of leishmaniasis can be established and treatment initiated. Appropriate management requires an accurate diagnosis, which often includes identification of the specific etiologic species. Different endemic areas have varying sensitivities to the same medication, even within individual species. Species identification may be of practical value, because infections with select species have a substantial risk of visceral involvement. In addition, HIV and otherwise immunocompromised patients with leishmaniasis have a propensity for diffuse cutaneous leishmaniasis. For most New World Leishmania species, parenteral antimonial drugs remain the first line of therapy, while Old World species are easily treated with physical modalities. Historically, live organism vaccination has been used and is effective in preventing leishmaniasis, but results in an inoculation scar and an incubation period that may last for years. A more effective method of vaccination would be welcome.