Visceral leishmaniasis (VL) represents the most severe form of the tropical disease, leishmaniasis. Treatment of VL is complicated because of the few clinically approved antileishmanial drugs available; emerging resistance to first-line drugs; need for a temperature-controlled ‘cold’ supply chain; serious toxicity concerns over drugs such as amphotericin B; high cost of medication; and unavailability of clinically approved antileishmanial vaccines. Attacking potential molecular targets, specific to the parasite, is a vital step in the treatment of this and other infectious diseases. As we discuss here, comprehensive investigation of these targets could provide a promising strategy for the treatment of visceral leishmaniasis.