Context: Leishmania is a pathogen that infects mononuclear phagocytes in which they establish chronic intracellular parasitism and survive for the infected person's lifetime. Untreated cases of visceral leishmaniasis (VL) could cause death within two years. Along with known complications of VL, co-infection of Leishmania with human immunodeficiency virus (HIV) is becoming more frequent, with important clinical, diagnostic, chemotherapeutic, epidemiologic, and economic implications. This review attempts to provide updated information about diagnosis and treatment of VL. Evidence Acquisition: In this narrative review, recent published sources of information on leishmaniasis consisting of books and articles have been reviewed. This review focuses on VL. Results: The outcome of infection depends on the host, the Leishmania species, and co-morbidities or co-infections. Disease manifestation may range from asymptomatic carrier to fatal disease. The development of a sensitive and rapid antigen detection test for relapse detection and also for cure remains an important aspect in diagnosis. Conclusions: Development of novel drugs and diagnostic tests has allowed us to better manage VL. Although leishmaniasis is one of the oldest known parasitic infectious diseases, increasing prevalence of VL among specific populations, recent reports of disease reactivation and flare-up in clinically asymptomatic patients after the onset of immunosuppressive therapy, the risk of disease acquisition by tourists in endemic areas (e.g., the Mediterranean eara), and difficulties in prevention and controlling disease (i.e., given the diversity and distribution of vectors and reservoirs), leishmaniasis has again attracted researchers' attention. Concerning reports of treatment failure and drug resistance are also new challenges in management of this parasitic disease in endemic areas.