Opioid effectiveness can be improved by individualizing dosing, route of administration and the drug. Particularly in the treatment of chronic non-cancer pain, careful patient selection is essential. The current review concentrates on new ideas about improving opioid effectiveness by increasing efficacy or reducing adverse effects by combining other drugs that modulate opioid receptor mediated effects. These pharmacological “oipoid adjuvants” include e.g. α₂-adrenergic agonists, non-steroidal anti-flammatory analgesics, NMDA-receptor antagonists, CCK-antagonists, gabapentinoids and NK-1 receptor antagonists. The theoritical background and the clinical evidence of these combinations will be discussed.