Preventing human-to-mosquito transmission of malaria parasites provides possible solutions to interrupt the malaria parasite life cycle for malaria elimination. The development of validated routine assays enabled the discovery of such transmission-blocking compounds. Currently, one development priority remains on combinations of dual-active compounds with equipotent activity against both the disease-causing asexual and transmissible, sexual erythrocytic stages. Additionally, transmission-blocking compounds that target gametocyte-specific biology could be used in combination with compounds against asexual parasites. In either case, preventing transmission will reduce the risk of reinfection and, if different processes are targeted, also curb the spread of drug resistance. Here, we provide an updated roadmap to the discovery and development of new antimalarials with transmission-blocking activity to guide drug discovery for malaria elimination. Malaria burden can be demonstrably reduced by blocking parasite transmission between the human host and mosquito vector.Antimalarial drugs that target blood-stage parasites as well as block onward parasite transmission will be useful for elimination strategies.Transmission-blocking activity that is associated with targeting different biological processes, or showing polypharmacology, will have obvious advantages in combination strategies to protect blood-stage actives from resistance transmission.Candidate drugs with equipotent activity against blood stages and transmissible stages have been identified and show promise in development as transmission-blocking strategies.