Abstract: Expression analysis and epidemiologic studies have provided indirect evidence that proteinases and growth factors play a role in the development of atherosclerosis and complications such as aneurysm formation and plaque rupture. Studies using genetically altered mice have proven to be an elegant tool to study the causal involvement of these factors in atherogenesis and to gain insight into the underlying mechanisms. Recently, proteinases of the plasminogen and matrix metalloproteinase (MMP) systems as well as their inhibitors have received much attention, and these studies together have emphasized the complexity of their role in vascular disease. This overview summarizes the current knowledge on plasminogen activator inhibitor‐1 (PAI‐1) in the progression of atherosclerosis and the influence of MMPs in aneurysm formation. In addition, a possible role for Gas6, the product of growth arrest‐specific gene 6, in atherosclerotic lesion development is put into perspective.