Antimicrobial resistance (AMR) in pathogens including protozoan parasites (particularly for malaria and leishmaniasis) is a major challenge to global disease control. The emergence and spread of resistance to frontline antimalarial drugs, including artemisinin-based combination therapies, and to key antileishmanial treatments such as antimonials and miltefosine, threaten recent gains in disease reduction. AMR in Plasmodium and Leishmania is driven by parasite genetic adaptation, altered drug transport and metabolism, and host–pathogen interactions that promote persistence and immune evasion. In my talk I will focus on the current understanding of resistance mechanisms and discuss emerging strategies to combat AMR, host-directed interventions, and immune-based approaches such as vaccines.