Cancer pain and pain associated with non-neoplastic diseases can be associated with pain mechanisms, such as a peripheral or central sensitization or deafferentation. The clarification allows indirect conclusions about the underlying mechanisms based on clinical signs, such as allodynia or hyperalgesia. Non-opioid analgesics are the basis of cancer pain therapy according to the World Health Organization (WHO) pain ladder. In the case of severe cancer pain, treatment can be escalated directly from level 1 to level 3. Opioids are highly effective for the treatment of cancer pain even with a neuropathic component, which can occur in up to 40 % of cases as amixed pain syndrome. Coanalgesics represent a valuable therapeutic adjunct for better pain control and can address treatment of comorbidities, such as anxiety, depression and sleep disorders. When liver and/or renal function is reduced, the dosage of many drugs has to be adapted. Treatment of multimorbid or critically ill patients with opioids and antidepressants/anticonvulsants requires consideration of numerous possible pharmacodynamic and pharmacokinetic interactions.