Acute rheumatic fever results from an immunological response to group A streptococcal infection, but the exact nature of this response, and of the underlying host and organism characteristics, continues to evade researchers. Earlier models of rheumatic fever pathogenesis emphasised the importance of humoral immunity, but more recent work suggests that cellular immunity may play a primary role. Greater understanding of these disease mechanisms is allowing researchers to move towards the development of a vaccine for rheumatic fever.