Substance use disorder (SUD) continues to pose a significant global health challenge, necessitating innovative and effective therapeutic interventions. Ketamine, traditionally recognized for its anesthetic properties, has emerged as a novel and promising avenue for the treatment of SUD. This narrative review critically examines the current body of literature surrounding the use of ketamine in various forms and settings for individuals grappling with substance abuse. The review explores the neurobiological underpinnings of ketamine’s potential therapeutic effects in SUD, shedding light on its impact on glutamatergic neurotransmission, neuroplasticity, and reward pathways. Special attention is given to the psychotropic and dissociative properties of ketamine, exploring their implications for both therapeutic outcomes and patient experience. Ultimately, this review aims to provide a comprehensive overview of the current state of knowledge regarding ketamine’s role in the treatment of SUD, emphasizing the need for further research and clinical exploration. As we navigate the complex terrain of addiction medicine, understanding the nuances of ketamine’s potential in SUD holds promise for the development of more effective and personalized therapeutic strategies.