The role of liquid chromatography coupled with mass spectrometry (LC-MS) techniques in routine therapeutic drug monitoring activity is becoming increasingly important. This paper reviews LC-MS methods published in the last few years for certain classes of drugs subject to therapeutic drug monitoring: immunosuppressants, antifungal drugs, antiretroviral drugs, antidepressants and antipsychotics. For each class of compounds, we focussed on the most interesting methods and evaluated the current role of LC-MS in therapeutic drug monitoring.