Dengue is the leading mosquito-borne viral illness infecting humans. Owing to the circulation of multiple serotypes, global expansion of the disease and recent gains in vaccination coverage, pre-existing immunity to dengue virus is abundant in the human population, and secondary dengue infections are common. Here, we contrast the mechanisms initiating and sustaining adaptive immune responses during primary infection with the immune pathways that are pre-existing and reactivated during secondary dengue. We also discuss new developments in our understanding of the contributions of CD4⁺ T cells, CD8⁺ T cells and antibodies to immunity and memory recall. Memory recall may lead to protective or pathological outcomes, and understanding of these processes will be key to developing or refining dengue vaccines to be safe and effective.