Liquid chromatography coupled to mass spectrometry nowadays plays an important role in the field of therapeutic drug monitoring (TDM), especially of new compounds for which no immunoassays are available. This paper reviews LC-MS(-MS) methods published recently for anti-infective drugs: antiretroviral drugs, other antiviral drugs, antibacterial drugs, antihelmintic drugs, antimalarial drugs, and other antiprotozoal drugs. An overview of the different methods is given, with special focus on selection of the internal standard and validation procedures.