Ivermectin (IVM) is the drug of choice for a variety of parasitic diseases due to its broad spectrum of activity and wide margin of safety. More than 18 million people are treated with IVM each year. Delivery modes include oral, topical, and s.c. injections. Its anti-parasitic activity depends upon species and developmental stages. Although IVM is believed to act mainly through interactions with invertebrate glutamate-gated chloride (GluCl) channel, other targets such as spleen cells and aminobutyric acid receptors may play important roles in the anti-parasitic activity of IVM. As several organisms have evolved resistance to IVM through mutations in p-glycoproteins and/or the GluCl channel itself, research continues on improvement of IVM either through mode of administration or the feasibility of alternative macrolides. An understanding of IVM's pharmacology is essential before improved therapeutics are created.