Restenosis is an important limitation of percutaneous coronary interventions (PCI). In-stent restenosis is mainly due to neointimal hyperplasia, a proliferative process modulated by inflammatory mechanisms. Numerous technical and pharmacological means have been tested to reduce restenosis rates, with frequently disappointing clinical results. Drug-eluting stents (DES) have demonstrated a high efficacy in reducing restenosis, but there are some associated problems that limit its generalized utilization. Glucocorticoids (GC), as potent anti-inflammatory agents, may exert beneficial effects on neointimal proliferation. Clinical studies with oral and intracoronary GC therapy have demonstrated reduction in restenosis rates in selected patients. Although further investigations are warranted, GC might have a potential role for restenosis prevention in selected cases.