Acetylsalicylic acid (ASA) hypersensitivity still represents one of the major deals for patients with atherosclerotic cardiovascular disease (ASHD), especially for those requiring percutaneous coronary interventions in the absence of validated alternative options. Despite symptoms after ASA administration being reported in 6–20% of cases, true ASA allergy only represents a minority of the patients, pointing to the importance of challenge tests and potential strategies for tolerance induction. ASA desensitization protocols were proposed several decades ago, with accumulating the literature on their use in patients undergoing PCI either for chronic disease or acute coronary syndromes. Nevertheless, the promising results of the studies and meta-analyses have not been validated so far by the support of large-scale randomized trials or unique indications from guidelines. Therefore, ASA desensitization is still largely unapplied, leaving the management of ASA hypersensitivity to the individualized approach of cardiologists.