Coronary stents are the mainstay of percutaneous coronary revascularization procedures and have significantly decreased the rates of acute vessel closure and restenosis. Stent thrombosis (ST) after percutaneous coronary intervention is an uncommon and potentially catastrophic event that might manifest as myocardial infarction and sudden death. Optimization of stent implantation and dual antiplatelet therapy have markedly reduced the occurrence of this complication. Bare-metal stent (BMS) thrombosis occurs in <1% of the cases, usually within the first month after implantation. The advent of drug-eluting stents (DES) has raised concerns regarding later occurrence of ST, beyond the traditional 1-month timeframe, especially in complex lesion subsets that were excluded from randomized trials that compared BMS to DES. There is widespread controversy regarding the actual incremental risk associated with DES. Recent studies suggest a 0.5% increased long-term thrombosis risk with DES; however, the clinical significance of these events remains under debate. The degree of protection achieved by dual antiplatelet therapy and optimal duration of treatment are under investigation. Novel stent designs might potentially decrease the incidence of this event. In this review, we will describe the current knowledge of the pathophysiology of late DES thrombosis, although many aspects remain incompletely understood.