Anti-trypanosomiasis vaccination still remains the best theoretical option in the fight against a disease that is continuously hovering between its wildlife reservoir and its reservoir in man and livestock. While antigenic variation of the parasite surface coat has been considered the major obstacle in the development of a functional vaccine, recent research into the biology of B cells has indicated that the problems might go further than that. This paper reviews past and current attempts to design both anti-trypanosome vaccines, as well as vaccines directed towards the inhibition of infection-associated pathology.