Restenosis after stent implantation is mainly characterized by an inflammatory response to the procedural injury and an intense fibrocellular response including smooth muscle cell (SMC) proliferation. After angioplasty alone, the restenosis process also involves thrombus formation and negative remodeling. Due to the pleiotropic mode of action exerted by glucocorticoids which include profound anti-inflammatory and immunosuppressive effects, direct inhibition on SMC proliferation and apoptosis, their potential in the prevention of restenosis has gained widespread interest. Over the last decade, preclinical and clinical data have not been able to conclusively document a robust therapeutic effect on restenosis after angioplasty or stent implantation. Only recently, preclinical data and limited observations in humans using drug eluting stents for local drug delivery have suggested beneficial effects of dexamethasone on neointimal proliferation. Randomized clinical trials using local drug delivery are expected to start in the near future. In the light of these ongoing developments, this review summarizes the pathophysiological basis of glucocorticoid action in the context of restenosis, provides an overview of the animal data available and discusses the clinical results that have been gathered over the last decade with particular emphasis on dexamethasone.