In resource-limited tropical settings, both impetigo and rheumatic disease are endemic. The major cause of impetigo in these regions is the group A streptococcus and there is a growing body of opinion implicating impetigo in the pathogenesis of rheumatic fever and rheumatic heart disease (RHD). This potentially has major implications for control of these neglected diseases, which account for at least 350 000 deaths worldwide, annually. In this review, we summarize recent advances in the epidemiology of group A streptococcal skin disease and examine evidence for the relationship between group A streptococcal skin disease and rheumatic fever. Detailed epidemiologic studies of impetigo, particularly among indigenous communities in the Pacific among whom rheumatic fever is endemic, find the disease remarkably prevalent. In contrast, group A streptococcal pharyngitis occurs no more frequently than in regions wherein rheumatic fever is now rare. Studies of molecular epidemiology reveal that overall there is a greater diversity of group A streptococcal strains in tropical regions, and skin-associated strains appear predominant. These skin strains may move between skin and throat, and there is increasing evidence of skin-associated strains being linked to cases of rheumatic fever. The available data support the hypothesis that group A streptococcal impetigo plays a role in the pathogenesis of RHD. There is considerable scope to investigate this question through studies of pathogenesis, employing advances in both human and bacterial genetics, molecular immunology, and carefully designed trials aimed at control of impetigo.