The formation of a fibrin clot is a pivotal event in atherothrombotic vascular disease and there is mounting evidence that the structure of clots is of importance in the development of disease. This review describes the crucial events in the formation and dissolution of a clot, with particular focus on genetic and environmental factors that have been identified as determinants of fibrin structure in vivo, and discusses the substantiation of the relationship between fibrin structure and disease in conjunction with a review of the current literature.