Acetylsalicylic acid, or aspirin (ASA), is widely used in patients with cardiovascular disease to prevent acute ischemic events. However, platelet response to ASA is not equal in all individuals, and a high variability in the prevalence of ASA resistance is reported in the literature (0.4-83%). Actually, ASA resistance is poorly understood; this stems from the fact that its definition is unclear, its presence can be evaluated by a number of assays that are not equivalent, and its prevalence may vary widely based on the population studied. This article (1) exposes the difficulties in defining ASA resistance; (2) discusses the mechanisms by which ASA resistance may occur; (3) presents the characteristics that may put patients at greater risk of exhibiting ASA resistance; and (4) discusses the clinical impact of ASA resistance in patients requiring chronic therapy.