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Background: A high prevalence of epilepsy has been observed in several onchocerciasis-endemic villages in the Sanaga River basin, Cameroon. Recent studies suggest that ivermectin, a drug that is distributed annually with the aim of eliminating onchocerciasis, may have a protective effect against acquiring onchocerciasis-associated epilepsy (OAE). This study, therefore, provides an in-depth understanding of both the complex therapeutic landscape for epilepsy as well as the experiences related to the 'community-directed treatment with ivermectin' (CDTI) campaign in order to identify a more trenchant path forward in the fight against epilepsy. Methodology/Principal findings: Based on a mixed methods study combining a qualitative strand with a quantitative survey, we found that epilepsy was perceived to have had an epidemic emergence in the past and was still considered an important health issue in the study area. Socio-economic status, availability and accessibility of drugs and practitioners, as well as perceived aetiology shaped therapeutic itineraries for epilepsy, which included frequenting (in)formal biomedical health care providers, indigenous and/or faith healing practitioners. Ivermectin uptake for onchocerciasis was generally well known and well regarded. The CDTI faced structural and logistical bottlenecks undermining equal access and optimal adherence to the drug. Conclusions/Significance: Uninterrupted, sustainable and comprehensive health-service delivery is essential to help alleviate the epilepsy burden on afflicted households. Addressing structural challenges of CDTI and communicating the potential link with epilepsy to local populations at risk could optimize the uptake of this potentially significant tool in OAE prevention. Author summary: Regions where onchocerciasis–a parasitical infection transmitted by blackflies–is endemic also tend to suffer from high levels of epilepsy. Recent studies suggest that ivermectin, an anti- onchocerciasis drug distributed annually to entire populations in onchocerciasis-endemic regions, may protect against developing onchocerciasis-associated epilepsy (OAE). As the link between onchocerciasis and epilepsy has been poorly understood and scientifically neglected in the past, our mixed methods research investigated how residents in an affected Cameroonian area perceive and cope with epilepsy; how they interpret the (causes of the) illness; where they seek care and why there. Armed with this knowledge, epilepsy control programs can optimize interventions geared at relieving the burden of epilepsy–and potentially OAE–which is essential given the fact that, despite 15–20 years of ivermectin distribution, onchocerciasis transmission persists and epilepsy prevalence in these regions remains high. Our findings illustrate how crucial it is to ensure uninterrupted, sustainable and comprehensive health service delivery for epilepsy. Furthermore, the structural challenges associated with the mass ivermectin distribution campaign must be addressed in order to relieve the burden of onchocerciasis, and potentially OAE. Without first addressing these structural bottlenecks, uptake and adherence to ivermectin treatment will remain insufficient. [ABSTRACT FROM AUTHOR]