Despite the growing off-label use of ketamine for depression and other psychiatric indications, its long-term safety profile and abuse potential remain unclear. We present a case of a patient who presented with paranoia and personality changes attributed to ketamine misuse, which illustrates the need for more robust screening and systematic monitoring with this medication. Continued evaluation of the abuse potential of ketamine in long-term treatment as well as restricted access and in-office administration are important, to develop a better understanding of the risk-benefit profile of this drug.