Visceral leishmaniasis (VL) is a life-threatening vector-borne parasitic disease is distributed in some parts of the new world and old world. The disease is endemic in different parts of Iran. This review article has been focused on major topics of epidemiological aspects and clinical features of VL in Iran for the period of 2002 through 2012. For the detection of VL in humans as well as animal reservoir hosts, anti-Leishmania antibodies were detected using direct agglutination test (DAT) as a validated serological test. Parasitological examinations were performed on suspected VL patients as well as canines and rodents. Different molecular methods were used for identification of species and genotype/ or strain of Leishmania spp. isolated from infected humans, animal reservoir hosts and vectors. Altogether, 1698 out of 36081 (4.7%) human serum samples collected from 5 distinct geographical zones showed anti-Leishmania antibodies at titers ≥ 1:3200 using DAT. The majority of VL cases in the endemic areas were found among children up to 12 years old. Almost 75% of DAT-positive cases (≥1:3200) in endemic areas showed clinical signs and symptoms. Predominant signs and symptoms in 217 hospitalized patients with DAT positive (≥1:3200) results included paleness (99.5%), fever (96.9%), splenomegaly (91.5%), hepatomegaly (53.6%) and lymphadenopathy (21.1%). Integrated VL surveillance system in primary care using DAT, could decrease mortality and morbidity of the disease in the VL endemic areas of the northwestern Iran. Out of 7204 serum samples collected from domestic dogs in various geographical locations of Iran, 879 (12.2%) were DAT sero-positive at titers ≥ 1:320. L. infantum as the principal causative agent of the disease was isolated from infected humans, domestic and wild canines and rodents. The principal animal reservoir hosts of the infection are domestic and wild canines. Ph. kandelakii, Ph. perfiliewi transcaucasicus, Ph. tobbi in northwestern Iran; Ph. major s.l. (=Ph. neglectus), Ph. keshishiani, and Ph. alexandri in southern parts of Iran were molecularly and/or parasitologically positive for L. infantum infections. The zoonotic form of VL (ZVL) caused by L. infantum occurs sporadically in all geographical zones of Iran but in northwestern and southern parts of the country the disease is endemic. DAT as an appropriate and potential tool has been used for sero-diagnosis and sero-epidemiological of VL among humans as well as domestic and wild canines.