A novel solventless sample preparation, stir-bar sorptive extraction (SBSE), for extraction, and sample enrichment of organic compounds from biological fluids, is described in this manuscript from principle to applications. The SBSE is based on sorptive extraction, whereby the compounds are extracted into a polymer coating, polydimethylsiloxane (PDMS), on a magnetic stirring rod. The extraction is controlled by the partitioning coefficient of drugs between the PDMS and sample matrix, and upon the sample-extraction medium phase ratio. The SBSE technique has been applied successfully, with high sensitivities, to biomedical analysis of volatiles and for semi-volatiles drugs from biological sample, including urine, plasma, and saliva. SBSE combined with in situ derivatization, drugs quite more polar (e.g. metabolites) also can be analyzed