Circumcision is the most common surgical procedure performed in the neonatal period in North America. If untreated, the pain of circumcision causes both short and long term changes in infant behaviours. The most widely studied pharmacological intervention for pain management during circumcision is dorsal penile nerve block (DPNB) by injected lidocaine (lignocaine). Randomised controlled trials have demonstrated its efficacy; infants premedicated with lidocaine have significantly smaller changes in physiological and pain-related behaviours compared with infants who are not given analgesics. A meta-analysis of injection-related adverse effects (bruising/haematoma) yielded a risk of 6.7% (95% confidence interval, 0.5 to 12.9%). Systemic toxicity from injected local anaesthesia has not been reported. Less effective modalities include topical anaesthesia with lidocaine-prilocaine cream [Eutectic Mixture of Local Anaesthetics (EMLA)], lidocaine cream and oral administration of sucrose. The good tolerability of lidocaine-prilocaine cream has been demonstrated by a lack of clinically significant methaemoglobinaemia when used appropriately. Nonpharmacological interventions (pacifier, specially designed restraint chair) reduce distress during the procedure, and paracetamol (acetaminophen) may provide postoperative analgesia. No single agent has been demonstrated to ameliorate pain for all infants undergoing circumcision. A multimodal approach of pharmacotherapy is currently recommended. Studies evaluating the efficacy of combined analgesia have demonstrated significant benefits for combinations of 2 or more forms of treatment (such as DPNB and sucrose-dipped pacifier) compared with single interventions. The instrument used to perform the circumcision is also important. The Mogen clamp has been shown to be associated with a shorter procedure time and less pain compared with the Gomco clamp. If circumcision is to be performed on infants, it is, therefore, recommended that combined analgesia and the Mogen clamp technique are used, and nonpharmacological stress reducing interventions such as pacifiers and comfortable restraining chairs should also be employed.