Therapeutic Drug Monitoring (TDM) is a clinical tool that uses the measurement of drug concentrations in biological fluids, primarily blood, to individualize patient pharmacotherapy. Its fundamental premise is that for a select group of drugs, a defined concentration range exists that maximizes therapeutic efficacy while minimizing the risk of toxicity. This chapter provides a comprehensive overview of TDM, beginning with its historical context and pharmacological principles. It outlines the key indications for TDM, which include drugs with a narrow therapeutic index, significant pharmacokinetic variability, and a well-established concentration-effect relationship. A systematic protocol for implementing TDM is detailed, encompassing the selection of the appropriate biological matrix, timing of sample collection, accurate assay methodology, and the crucial step of clinical interpretation. The chapter also critically examines the limitations of TDM, including assay variability, pre-analytical errors, and the pitfalls of misinterpreting drug concentrations without considering the patient’s clinical status. Finally, it explores the common clinical situations where TDM is routinely employed, such as in the management of epilepsy, prophylaxis of transplant rejection, and treatment of severe infections, highlighting its role in achieving precision medicine at the bedside.