The ?-blockers are among the most prescribed drugs for the treatment of cardiovascular diseases in the world. They have been mainly applied to the treatment of hypertension, heart failure, myocardial infarction and cardiac arrhythmias. Also, due to their massive use, ?-blocker pharmaceutical residues have been recently detected in environmental waters. Once released into the natural environment by Waste Water Treatment Plants (WWTPs), residues of ?-blockers can accumulate in aquatic media and aquatic species. Therefore, a great number of research studies have been carried out on their ecotoxicity for aquatic organisms, and potential risks for human health. The ?-blockers are also used as doping agent by athletes and illegally injected to animals in order to reduce their mortality. Therefore, it was essential to develop appropriate analytical procedures to provide reliable data related to their presence and concentrations in various matrices. The present study investigated the development of analytical approaches of ?-blockers reported in the literature between 2000 and 2022, and their occurrence in different matrices with also a focus on sample extraction procedures.