Stroke is a leading cause of death and disability worldwide. Aspirin is the most commonly used antiplatelet drug in both primary and secondary prevention of cerebrovascular and cardiovascular diseases. A proportion of patients may have stroke recurrence while they are on treatment with aspirin, giving rise to term aspirin resistance or aspirin failure. Studies have suggested that such recurrence could partly be attributed to biochemical aspirin resistance, with an estimated prevalence ranging between 5% and 65% among patients with ischemic stroke in the published studies. Common methods to evaluate laboratory aspirin resistance include light transmission aggregometry, PFA-100, VerifyNow-Aspirin assay, serum thromboxane B2, and urinary 11-dehydrothromboxane B2. Aspirin resistance is multifactorial in origin and involves diverse environmental and genetic factors, including single-nucleotide polymorphisms, miRNAs, drug interactions, and co-morbid risk factors. The current review overviews the concept of aspirin resistance, its evaluation and relationship with stroke recurrence, its outcome, and its implications on stroke management in the future.