Altered behavior of vascular smooth muscle cells (VSMCs) plays an important role in cardiovascular diseases including atherosclerosis and restenosis. Accelerated VSMC proliferation and migration lead to thickening of the intima and enhanced VSMC apoptosis leads to atherosclerotic plaque rupture and clinical symptoms of atherosclerosis. Consequently, the underlying mechanisms for this altered VSMC behaviour is of great interest. It is well established that the Wnt signaling pathways are critical for embryogenesis and development. In recent years an important role of the Wnt signalling pathways in vascular disease has emerged and is supported by observations of essential Wnt signalling in vascular development. In our laboratory we have investigated the role of Wnt proteins in the regulation of VSMC behaviour. We have demonstrated that Wnt proteins enhance intimal thickening. Interestingly, Wnts have differing effects on VSMCs; Wnt4 promotes proliferation, whilst Wnt2 augments migration. Moreover, we have identified that Wnt proteins act as survival factors for VSMCs and retard VSMC apoptosis at least in part by the up-regulation of WISP-1 (Wnt-inducible secreted protein-1). In summary, it is apparent that Wnts have divergent effects on VSMC behaviour and a greater understanding of Wnt pathways may reveal new therapeutic targets for vascular disease.