The benefits of ketamine in reducing pain are largely based on case reports and small clinical trials. We present a case series describing the application and efficacy of subanesthetic doses of ketamine in the treatment of complex pain syndromes poorly responsive to escalating doses of opioids. The discussion that follows suggests that subanesthetic intravenous ketamine can be used to successfully treat severe pain of different etiologies refractory to opioid dose escalation. Optimal dosing titration, duration of initial treatment, and the role of maintenance ketamine need to be further elucidated. Our case series adds to the extant literature supporting the role of subanesthetic ketamine for refractory pain problems.