Ebola virus disease kills more than half of people infected. Since the disease is transmitted via close human contact, identifying individuals at the highest risk of developing the disease is possible on the basis of the type of contact (correlated with viral exposure). Different candidates for post-exposure prophylaxis (PEP; ie, vaccines, antivirals, and monoclonal antibodies) each have their specific benefits and limitations, which we discuss in this Viewpoint. Approved monoclonal antibodies have been found to reduce mortality in people with Ebola virus disease. As monoclonal antibodies act swiftly by directly targeting the virus, they are promising candidates for targeted PEP in contacts at high risk of developing disease. This intervention could save lives, halt viral transmission, and, ultimately, help curtail outbreak propagation. We explore how a strategic integration of monoclonal antibodies and vaccines as PEP could provide both immediate and long-term protection against Ebola virus disease, highlighting ongoing clinical research that aims to refine this approach, and discuss the transformative potential of a successful PEP strategy to help control viral haemorrhagic fever outbreaks.