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River blindness (onchocerciasis) causes severe itching, skin lesions, and vision impairment including blindness. More than 99% of all current cases are found in sub-Saharan Africa. Fortunately, vector control and community-directed treatment with ivermectin have significantly reduced morbidity. Studies in Mali and Senegal proved the feasibility of elimination with ivermectin administration. The treatment goal is shifting from control to elimination in endemic African regions. Given limited resources, national and global policymakers need a rigorous analysis comparing investment options. For this, we developed scenarios for alternative treatment goals and compared treatment timelines and drug needs between the scenarios. Control, elimination, and eradication scenarios were developed with reference to current standard practices, large-scale studies, and historical data. For each scenario, the timeline when treatment is expected to stop at country level was predicted using a dynamical transmission model, and ivermectin treatment needs were predicted based on population in endemic areas, treatment coverage data, and the frequency of community-directed treatment. The control scenario requires community-directed treatment with ivermectin beyond 2045 with around 2.63 billion treatments over 2013–2045; the elimination scenario, until 2028 in areas where feasible, but beyond 2045 in countries with operational challenges, around 1.15 billion treatments; and the eradication scenario, lasting until 2040, around 1.30 billion treatments. The eradication scenario is the most favorable in terms of the timeline of the intervention phase and treatment needs. For its realization, strong health systems and political will are required to overcome epidemiological and political challenges. Author Summary: River blindness (onchocerciasis) is transmitted by blackflies and causes severe itching, skin lesions, and vision impairment including blindness. More than 99% of all current cases are found in sub-Saharan Africa where the disease has historically hindered socioeconomic development in endemic areas. The treatment goal is shifting from control to elimination in Africa as morbidity has significantly decreased through vector control and community-directed treatment with ivermectin. Studies in Mali and Senegal proved that elimination is feasible with ivermectin administration. Given limited resources, national and global policymakers need a rigorous analysis of investment options from epidemiological, economic, and societal aspects. For this, we developed control, elimination, and eradication scenarios and compared treatment timelines and drug needs over the next 30 years. We found that the elimination and eradication scenarios would require a shorter treatment phase and a smaller amount of ivermectin than the control scenario, mainly because community-directed treatment with ivermectin could be ended earlier thanks to regular active surveillance. [ABSTRACT FROM AUTHOR]