Medications are substantial tools for the prophylaxis, treatment, and maintenance of the population’s health. The development of different pathologies and public health issues leads to the varied use of certain types of medications, such as antibiotics, analgesics, anti-inflammatories, neural regulators, etc. However, most medications have the potential to cause side effects in diagnosed patients. Therefore, with the continuous use of these agents, it is important to recognize evidence of changes in the immune response that impact the development of different clinical manifestations and states associated with hypersensitivity, hyperreactivity, and toxicity of these substances in the body. This is a result of the formation of artifacts associated with metabolism, capable of inducing sensitization of protein mediators that exacerbate cellular responses on biological targets. As a result, an approach to the main general aspects, molecular mechanisms, and description of clinical entities associated with allergy and toxicity to widely used medications, such as non-steroidal anti-inflammatory drugs, β-lactam antibiotics, and anticonvulsants, was carried out. These medications have been linked to numerous clinical responses that are of significant interest to the academic and research community.