Percutaneous transluminal angioplasty, with or without stenting, is widely used for patients with coronary and peripheral arterial occlusive disease. However, the development of restenosis endangers long-term success. The process of restenosis has been the subject of research focusing mostly on the coronary and less on the peripheral arteries. Restenosis after stenting is the result of a healing process due to traumatic vascular wall injury, caused by stent implantation and involves the release of several growth factors as well as cytokines. The denudation of the vascular wall endothelium occurring during angioplasty and stenting is the primary step inducing the cascade of events leading to restenosis. Following that, four distinct phases have been observed, including focal thrombosis, inflammation, cellular proliferation characterized by neointimal hyperplasia (NIH) and vessel remodeling. The molecular and cellular basis of restenosis after percutaneous interventions suggests that events taking place in this process are moderated by the elaborate interplay of the following systems: (1) platelet activation and related growth factors and pro-inflammatory cytokines; (2) leukocyte activation; (3) activation of the coagulation-fibrinolysis system; and (4) events at the platelet surface. Numerous mediators, such as growth factors, cytokines, chemokines, adhesion molecules and extracellular matrix proteins are involved in restenosis. Further research on medical and other treatment modalities are underway in an attempt to control neointimal hyperplasia, reduce restenosis rates, and eventually improve long-term success of percutaneous treatment of vascular occlusive disease.