The development of cardiovascular disease is influenced by complex interactions between environmental and genetic factors. Despite a flurry of activity in the past decade to identify common genetic variants that predispose to cardiovascular disease the results have, on the whole, been inconclusive. In the present review we summarise the available information regarding genetic variants of fibrinolytic factors and discuss the issues pertinent to understanding the inconsistencies in their reported relationship to cardiovascular disease. Finally, we suggest that work in this area should continue, but with the emphasis firmly directed towards the use of genetic markers as tools for investigating and understanding the complexities of cardiovascular disease.