Current practice predicates the use of multiple drug combinations in the treatment of neuropathic pain. These combinations may be required because of multiple pain symptoms directly arising from neuropathic pathology, other symptoms attributable to the chronicity and severity of the patient's pain or conditions unrelated to their pain. A fear exists that combination drug use or the addition of a new drug to a therapeutic regimen may lead to increased drug toxicity or decreased efficacy. Many of the drug interactions of significance to neuropathic pain physicians involve the cytochromes P450 2D6 and 3A3/4 isoenzymes. Drug interactions should be more predictable based on the knowledge of which compounds induce, inhibit or are metabolized by specific cytochrome P450 enzymes. Mechanisms of induction or inhibition of biotransformation via the P450 hepatic enzyme system are discussed and various inducers, inhibitors and substrates relating to neuropathic pain pharmacotherapy are listed.