The goal of the present research has been to develop a selective analytical detection procedure for the easy identification and assay of drugs and related substances present in complex mixtures, without a chromatographic separation step or other work up. The detector of choice is circular dichroism (CD) spectropolarimetry which has the appropriate balance between degree of analytical selectivity and breadth of application. Applications that are described are selected from work carried out in the context of forensic, clinical, and pharmaceutical chemistries, and specifically include discussions of the analyses of enantiomeric mixtures of nicotine and cocaine, the D and E vitamins, and cholesterol and other steroids.