Adverse effects of opioids are multiple. They are most often receptor-mediated and inseparable from their desired effects. The most severe mishaps with opioids are related to their respiratory depressant effect, which is widely influenced by factors such as pain, previous opioid experience and awareness. Other relevant central nervous system effects of opioids include cough suppression, nausea and vomiting, rigidity, pruritus and miosis. The cardiovascular adverse effects of opioids are mainly related to histamine release and differ widely between agonists and agonist-antagonists. Gastrointestinal effects such as constipation, reflux and spasms of the bile duct are well described. Adverse effects on endocrine, immunological and haematological functions are possible, while allergic reactions are extremely rare. The adverse effects of long term use are overestimated. Systemic toxicity is negligible and development of tolerance is minimal while treating pain. In the clinical setting of pain control, addiction and withdrawal do not pose significant problems. Nevertheless, the possible effects of opioids on the unborn child should always be considered. Overall, opioids show a good record of safety. Their use should not be unduly limited by unfounded fears of adverse effects, but these effects should be avoided by anticipation and prevention.