Depression is the most common mental disorder in the world and one of the top ten causes of morbidity and mortality (Berton and Nestler, 2006; Nestler et al., 2002). 20% of the world's population is affected by depression at some point in their lives, while 4% of men and 8% of women are affected by a clinically significant depressive disorder. However depressive symptoms in general are much more common (Lehtinen, V and Joukamaa, M 1994). While depression came in second on the list of most disabling disorders when measured in terms of years lived with disability, the WHO predicted it would be the number one health problem in the next 20 years. (Leonard BE and Cryan JF). Unfortunately, currently available antidepressants take weeks or months to start working. However, the percentage of respondents during this period ranges from 30 to 60% (Trivedi et al, 2006 ref). More recently, ketamine has shown rapid onset and sustained antidepressant activity, a game changer that may revolutionize antidepressant treatment strategies and outcomes. This article will evaluate the effectiveness of ketamine compared to standard antidepressants and highlight its potential as a prototype for a new generation of fast-acting antidepressants. In the early 20th century, treatment strategies for depression ranged from invasive therapies such as insulin coma therapy, to chemical and electrical shock therapy. to the administration of some addictive chemicals such as chloral hydrate, barbiturates, amphetamines and opiates (Lopez-Munoz & Alamo C, 2009). In the 1950s, ipronizide, previously used as an antituberculosis, was introduced as the first monoamine oxidase inhibitor (MAOI) and the first antidepressant ever marketed. Then imipramine was inserted…in the middle of the sheet of paper…in an elevated maze and social interaction test in Wistar rats. Depress Anxiety 5(1), pp 29−33.Simon GE, Savarino J, Operkalski B, Wang PS, (2006), Risk of suicide during antidepressant treatment. ,I am. J. Psychiatry.,163, pp 41-47.Trivedi MH, (2006), Outcome evaluation with citalopram for depression using measurement-based care in STAR*D implications for clinical practice. AmJ Psychiatry, 163(1): pp 28-40Liu and aghanian 2008Zarate CA, Du J., Quiroz J., Gray NA, Denicoff K., Singh JB, et al. (2003). Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: role of the glutamatergic system. Ann NY Acad Sci 1003, 273−291.Zarate C, Singh J, Manji HK (2006) Cellular plasticity cascades: targets for the development of new therapies for bipolar disorder. , Biol. Psychic. 59, page 1006-1020.