Alkylation, acylation, silylation and other derivatization reactions applied to the gas chromatographic analysis of drugs in biological matrices are reviewed. Reaction conditions are discussed in relation to reaction mechanisms. Detector-oriented labelling of drugs, and derivatization with chiral reagents for the separation of enantiomers are surveyed. Data on the sample clean-up, derivatization and GLC analysis of more than 300 drugs and related compounds are listed.