Ketamine is now frequently used in the management of chronic pain refractory to conventional treatments. However, its efficacy and adverse effects appear variable in the literature in line with heterogeneous methodologies and modes of administration, leading to controversy regarding the actual interest of ketamine for chronic pain treatment. A need for clinical trials on larger cohorts of well selected patients but also real-life studies to more accurately quantify its efficacy, refine its prescription dosages and better understand its long-term adverse effects is highlighted in the literature. Progress in this direction has been achieved in recent years with improved recommendations for use, taking into account different trajectories of analgesia with ketamine, depending on the etiology of the pain, and the psycho-affective profile of patients. A holistic approach is clearly needed with consideration of pain and depression comorbidities to optimize pain management.