Since the year 2000, ketamine and its enantiomers have been studied for their antidepressant effects. This paper will briefly summarise the journey of ketamine from an anaesthetic to an antidepressant. The text will present the key mechanisms of its action, as well as the actions of its metabolites. The aim of this article is to describe the role of specific groups of receptors in activation of important metabolic pathways and in production of factors such as mammalian target of rapamycin kinase (mTOR) and brain-derived neurotrophic factor (BDNF), in order to comprehensively present a potential link between ketamine, ketamine’s enantiomers and its metabolites with terms such as neuroplasticity and antidepressant action. Another important part of this article is a summary of arguments for and against importance of specific mechanisms of ketamine action and to compare (S) and (R)-ketamine’s potential to act as an antidepressant. This article may be particularly helpful for researchers in determining further research directions and serve as a summary of the current state of knowledge regarding the mechanisms of ketamine’s action and the latest therapeutic possibilities in the treatment of affective disorders.