According to the WHO report approximately 450 million people suffer from mental and behavioural disorder. Depression is one of the most common neurodegenerative disorders which arise due to the imbalance of neurotransmitters release at the synaptic cleft. A large number of synthetic drugs are being used as standard treatment for depression, they have many adverse effects that a limit the therapeutic treatment. Traditionally herbs are used for the treatment of depression which may offer advantage in terms of safety and tolerability, possibly by improvement in patient compliance. Herbal drugs are more commonly used because these have small amount of chemicals, these produced less side effects than standard drugs. Overall, this chapter presented an overview of the research that has been done on the many herbs, Mechanism of action involving monoamine reuptake, neuroreceptor binding and channel transporter function, and neural communication or HPA modulation. Several pharmaceutical companies are working on “triple” reuptake inhibitors that stop all three monoamines from being reabsorbed. Studies into the interplay of monoamine systems with other neurotransmitters (e.g., CRF, neurokinins, glutamate, and GABA etc.) will aid in the development of realistic, integrated neurochemical models of depression.