Benzodiazepines are used as hypnotics, tranquilizers, anticonvulsants or muscle relaxants whereas antidepressants are used for the treatment of psychiatric disorders such as depression. Antidepressants also possess tranquilizing properties. Many of the benzodiazepines are also used in combination with antidepressants in the management of depression. For the medical treatment of depression and neurosis, the concomitant administration of tricyclic antidepressants and benzodiazepines is widely used. A unique HPLC-UV method has been developed for the simultaneous quantitation of 1,4-benzodiazepines along with tricyclic antidepressants in biological fluids after SPE or sequential SPE fractionating them into two different groups. This unique methodology may be especially advantageous for routine determination in forensic and clinical investigations, and applicable for the quantitative determination of both substances in two-component tablet formulations. Book also comprises brief discussion on structure, properties and the effects of tricyclic antidepressants, HPLC technique, review on biological sample preparation and determination of these drugs by different methods.