Initial clinical trials in 1980 showed that ivermectin was remarkably effective against Onchocerca volvulus. Some 25 years after more than 50 million people are treated annually with Mectizan mainly within the framework of the African Programme for Onchocerciasis Control (APOC). This success has been possible thanks to Merck Mectizan Donation Program and to distribution through a novel strategy based on the strong involvement of endemic communities. In the last few years Mectizan has been used in combination with albendazole to control lymphatic filariasis on a large-scale basis in African countries. More recently ivermectin (under the tradename Stromectol) received market approval in France for treatment of gastrointestinal strongyloidiasis and scabies. Clinical trials are under way to evaluate the activity of ivermectin on nematodes (Loa loa, Mansonella sp., intestinal nematodes, cutaneous and visceral larva migrans) and ectoparasites (Pediculus humanus capitis, Phtirius pubis, Tunga penetrans, myiases). Trials are also ongoing to explain the mechanisms underlying the severe adverse events sometimes observed in patients presenting high Loa loa microfilaraemia and to develop preventive measures. Fundamental research will provide a better understanding of the mode of action of ivermectin at the molecular and cellular level, evaluate the risk of resistance of human parasites, and to determine the extent to which ivermectin could be used in association with other agents for the treatment of nonparasitic diseases.