Solid phase micro-extraction was originally designed as a technique for the solvent-free analysis of volatile organic contaminants in environmental samples. However, a wide variety of applications are now being pursued, including the analysis of drugs from a variety of matrices. In this review, the analysis of drugs by SPME from biological and related matrices, including water, urine, blood, hair and saliva, is discussed. A general overview of the special problems and techniques involved in SPME from biological matrices is presented, along with specific references and discussion of the analysis of many types of drugs and metabolites. It is seen that SPME is a highly versatile and flexible technique for these analyses.