The efficacy of aspirin to prevent thrombotic events in cardiovascular patients is well established, with >100 randomized trials having been conducted in high-risk patients and demonstrating a reduction in vascular death of approximately 15% and a further reduction in non-fatal vascular events of approximately 30%. While the benefit of aspirin is undisputed, it is also known that aspirin is associated with a dose-dependent increase in the risk of bleeding. It follows that most treatment guidelines advocate the use of the lowest aspirin dose effective in preventing thrombotic complications to minimize the risk of major bleeding. From this, a need for monitoring of aspirin therapy has emerged and prompted the development and investigation of numerous assays of platelet function. The intention behind monitoring of aspirin's antithrombotic effects is to maximize benefit and to personalize treatment based on individual patient characteristics. This article reviews the recent literature on the usefulness of platelet function testing in patients requiring aspirin; the variability of platelet reactivity in patients taking aspirin and its clinical impact; the potential mechanisms underlying suboptimal platelet inhibition by aspirin and future directions in terms of management of aspirin therapy.