The matrix metalloproteinases (MMPs) can degrade a range of extracellular matrix proteins and have been implicated in connective tissue destruction and remodelling associated with cancer invasion and metastasis, cartilage destruction in arthritis, atherosclerotic plaque rupture, and the development of aneurysms. Recently, naturally occurring sequence variation has been detected in the promoter of a number of MMP genes. These genetic polymorphisms have been shown to have allele-specific effects on the transcriptional activities of MMP gene promoters, and to be associated with susceptibility to coronary heart disease, aneurysms and cancers. These findings indicate that variation in the MMP genes may contribute to inter-individual differences in susceptibility to these common, complex diseases, likely through effects on the balance between the synthesis and degradation of extracellular matrix proteins.