The control of river blindness (onchocerciasis), a human disease transmitted by black flies, has been an economic and public health success in West Africa. It involved insecticide applications to as many as 50,000 km of rivers, almost weekly, in 11 countries between 1974 and 2002. The long-term biomonitoring of the effects of insecticide use on the nontarget invertebrate (primarily insect) and fish communities was initially designed on the basis of limited knowledge available for West African rivers and on information from other areas. Routine monitoring surveys demonstrated little effect on fish but produced inconclusive results for invertebrates. Research conducted beyond these surveys and current views in river and general ecology indicate that permanent damage to invertebrates from insecticiding was unlikely. The scientific progress made during the 29 years of this biomonitoring program is relevant to future, large-scale, long-term programs worldwide.