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Stent thrombosis (ST) is a life-threatening, although quite rare, complication of percutaneous coronary intervention with stenting. According to the Academic Research Consortium, it may be defined as definite, probable, or possible. Moreover, its occurrence after index procedure differentiates between early, late and very late. This complication is associated with high morbidity and mortality and has a very high impact on global health of patients with cardiovascular disorders, therefore a multifactorial approach seems a useful tool for understanding its causes and improving its outcome. In this review we analyze all the most important issues of this disorder beginning from its classification, then we overview the pathophysiological mechanisms and factors implicated and, lastly, we give a glimpse to the future perspective on prevention strategies.