Tegumentary leishmaniasis, comprising the cutaneous and mucocutaneous forms, is caused by at least 13 dermotropic species of protozoa of the genus Leishmania, most of which are prevalent in the New World. Although diseases in the Old and New Worlds share similar characteristics, the ultimate manifestations and severity are quite different, with more severe forms associated with mucosal lesions observed in the New World. For the diagnosis and treatment of leishmaniasis, differences based on clinical features, usefulness/sensitivity of diagnostic methods and therapeutic responses are mainly emphasized. We present a critical review of the diagnostic methods, their contribution and the necessity for their improvement/development, particularly in molecular diagnosis aimed at detection and species identification, as well as serodiagnosis. In addition to a review of the drugs currently utilized, we describe differences in their effectiveness in Old and New World leishmaniasis. HIV/Leishmania coinfection is also presented in the context of diagnosis and treatment.