The continuing need for sensitive and specific analytical methods for the detection and quantitation of cocaine is reflected by the number of publications that continue to be devoted to this topic. This review focuses on immunoassay-screening methods as well as chromatographic methods that were reported over approximately the last two decades for the determination of cocaine analytes in various biological specimens. Illicit cocaine analysis is addressed briefly in the introduction. The reviewed methods are summarized in tables to provide additional information on each assay. Solid-phase extraction was the most frequently applied technique to isolate cocaine analytes from biological matrices. Also, it was no surprise that gas chromatography-mass spectrometry operated in the positive ion-electron impact ionization mode was the most widely reported instrument used for the detection of cocaine analytes. However, other analytical methodologies, such as liquid chromatography-mass spectrometry, are becoming more important for the analysis of cocaine with the growing interest in identifying and quantitating multiple cocaine analytes with varying physiochemical properties.