The baboon model of schistosomiasis has been used extensively to study parasite biology, immune responses and pathological manifestations after natural and experimental infections. The body of knowledge accumulated so far has placed this animal model at the pinnacle in the continuing search for new interventions and might hold the key to the development of new anti-schistosome vaccines. In this review paper, we highlight previous and recent studies that have elevated the baboon to be the model of choice for schistosomiasis research. In particular, the long-term studies of re-infection after chemotherapy as well as the interaction between vaccination, chemotherapy and infection are highlighted.