Acetyl salycilic acid (ASA) has demonstrated beneficial effects in the management of subjects with increased risk of thromboembolism. Previous studies has proposed that an important number of subjects have a sub-optimal anti-aggregate response to this drug and higher risk of presenting an atherotrombotic episode, even while receiving the appropriate dose. Multiple etiologies have been proposed to explain this situation to which different farmacodynamic and farmacoquinetic entities could be related. There is no consensus about atherothrombotic the most appropriate technique to assess platelets' response to the ASA, the prevalence of this entity has not been determined. Even though, this resistance might be suspected in every subject with an atherothrombotic episode when receiving adequate dosage of ASA. The appropriated diagnosis and treatment of these of entities can turn into a real challenge. The aim of this study is to review the origin and recent diagnostic methods, classifications, and therapeutic alternatives for ASA resistance.