Background Cholera epidemics occur frequently in low-income countries affected by concurrent humanitarian crises. Evaluations of these epidemic response remains largely unpublished and there is a need to generate evidence on response efforts to inform future programmes. This review of MSF cholera epidemic responses aimed to describe the main characteristics of the cholera epidemics and related responses in these three countries, to identify challenges to different intervention strategies based on available data; and to make recommendations for epidemic prevention and control practice and policy. Methods Case studies from the Democratic Republic of Congo, Malawi and Mozambique were purposively selected by MSF for this review due to the documented burden of cholera in each country, frequency of cholera outbreaks, and risk of humanitarian crises. Data were extracted on the characteristics of the epidemics; time between alert and response; and, the delivery of health and water, sanitation and hygiene interventions. A Theory of Change for cholera response programmes was built to assess factors that affected implementation of the responses. Results and conclusions 20 epidemic response reports were identified, 15 in DRC, one in Malawi and four in Mozambique. All contexts experienced concurrent humanitarian crises, either armed conflict or natural disasters. Across the settings, median time between the date of alert and date of the start of the response by MSF was 23 days (IQR 14–41). Almost all responses targeted interventions community-wide, and all responses implemented in-patient treatment of suspected cholera cases in either established health care facilities (HCFs) or temporary cholera treatment units (CTUs). In three responses, interventions were delivered as case-area targeted interventions (CATI) and four responses targeted households of admitted suspected cholera cases. CATI or delivery of interventions to households of admitted suspected cases occurred from 2017 onwards only. Overall, 74 factors affecting implementation were identified including delayed supplies of materials, insufficient quantities of materials and limited or lack of coordination with local government or other agencies. Based on this review, the following recommendations are made to improve cholera prevention and control efforts: explore improved models for epidemic preparedness, including rapid mobilisation of supplies and deployment of trained staff; invest in and strengthen partnerships with national and local government and other agencies; and to standardise reporting templates that allow for rigorous and structured evaluations within and across countries to provide consistent and accessible data.