OBJECTIVE Traditionally, therapeutic drug monitoring has been used for the management of epilepsy, cardiac arrhythmias, asthma and depression. This review provides an update, particularly for the newer clinical applications, and how therapeutic drug monitoring (including use of analytical and interpretation tools) can improve clinical outcomes. RESULTS Improved drug assay methodologies and a greater understanding of pharmacokinetic and pharmacodynamic mechanisms has allowed the use of therapeutic drug monitoring for immunosuppressant drugs in organ transplant recipients, antiretroviral agents for HIV/AIDS and antimetabolite drugs for leukaemia. In addition, new computer software to analyse drug concentrations in complex populations is being developed and introduced into routine clinical applications to allow increasingly patient-specific assay interpretation. CONCLUSIONS Therapeutic drug monitoring assists in improving clinical success rates and minimizing toxicity. The use of therapeutic drug monitoring is therefore likely to become more widespread as new modalities are adopted.