Therapeutic drug monitoring (TDM) is a fundamental tool when administering drugs that have a limited dosage or high toxicity, which could endanger the lives of patients. To carry out this monitoring, one can use different biological fluids, including blood, plasma, serum, and urine, among others. The help of specialized methodologies for TDM will allow for the pharmacodynamic and pharmacokinetic analysis of drugs and help adjust the dose before or during their administration. Techniques that are more versatile and label free for the rapid quantification of drugs employ biosensors, devices that consist of one element for biological recognition coupled to a signal transducer. Among biosensors are those of the optical biosensor type, which have been used for the quantification of different molecules of clinical interest, such as antibiotics, anticonvulsants, anti-cancer drugs, and heart failure. This review presents an overview of TDM at the global level considering various aspects and clinical applications. In addition, we review the contributions of optical biosensors to TDM.