The recently described complication of late and very late stent thrombosis with coronary stents has raised the question of when is it safe to stop antiplatelet therapy in the era of drug eluting stents? With several million patients having already had coronary stents implanted worldwide, the importance of an appreciation of stent thrombosis is not only critical to the cardiologist but also surgeon, physician, dentist and other specialists that perform procedures on patients which require with-holding antiplatelet agents. Currently there is great concern amongst medical professionals on how to manage this group of patients in the absence of clear guidelines. This article reviews the current data on coronary stents, in-stent restenosis and stent thrombosis and role of antiplatelet medication post percutaneous coronary intervention (PCI) to provide a concise and clear algorithm for managing perioperative antiplatelet therapy in patients having undergone recent PCI. The algorithm encourages a multidisciplinary approach and is based on the surgical bleeding risk, operative risk of adverse cardiac events and stent thrombosis risk to guide safe practice. Challenging areas including aspirin and clopidogrel hypersensitivity, clopidogrel resistance and concomitant vitamin K antagonist therapy are also addressed.