The purpose of analysis of plasma and serum samples is to obtain knowledge about the concentration of drug substances and their metabolites in the circulating blood system. This chapter provides different examples related to analysis of plasma and serum samples. Whole blood samples cannot be injected directly into liquid chromatography (LC) or gas chromatography (GC), as they will immediately clog and deteriorate the injection systems and the chromatographic columns. Identification and quantification of drug substances in dried blood spots (DBS) are becoming increasingly popular, especially in the pharmaceutical industry. Urine samples are often used in forensic toxicology laboratories and in doping analysis laboratories for identification of drugs and drugs of abuse. For LC and LC-MS, the major purpose of sample preparation is to avoid loading the systems with matrix components, which can sacrifice instrumental stability. Saliva samples are very attractive in the field of forensic toxicology.