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A high prevalence of epilepsy is reported in many onchocerciasis-endemic regions. In this paper we discuss recent epidemiological and clinical aspects as well as public health implications of onchocerciasis-associated epilepsy (OAE) and propose a strategy to reduce the burden of disease. OAE probably presents in a variety of clinical manifestations, including the nodding syndrome and the Nakalanga syndrome. The most common clinical presentation, however, is generalized (primarily tonic-clonic) seizures. A characteristic of OAE is the onset of seizures between the ages of 3 and 18 years and clustering in certain families and villages close to rapid-flowing black-fly-infested rivers. A strategy combining active surveillance for epilepsy with early treatment with antiepileptic drugs and prevention of onchocerciasis by increasing the geographical and therapeutic coverage of community-directed treatment with ivermectin (CDTi) may considerably decrease the burden of disease.