Regional anesthesia provides effective anesthesia and pain relief in infants with age-specific data attesting to safety and efficacy. Regional anesthesia decreases exposure to opioids and general anesthetic agents and associated adverse drug effects, suppresses the stress response, and provides better hemodynamic stability compared to general anesthesia. Regional anesthesia can prevent long-term behavioral responses to pain. As a result, the overall number and variety of nerve blocks being used in infants is increasing. While neuraxial blocks are the most common blocks performed in infants, the introduction of ultrasound imaging and a better safety profile has advanced the use of peripheral nerve blocks. Infant-specific pharmacokinetic and pharmacodynamic data of local anesthetic medications are reviewed including risk factors for the accumulation of high serum levels of unbound, pharmacologically active drug. Bupivacaine accumulates with continuous infusion and 2-chloroprocaine can be used as an alternative. Local anesthetic systemic toxicity has the highest incidence in infants less than 6 months of age and is associated with bolus dosing and penile nerve blocks. Local anesthetic toxicity is treated by securing the airway, suppression of seizure activity and implementation of cardiopulmonary resuscitation. Administration of intralipid (intravenous lipid emulsion) is initiated at the first sign of toxicity. A high level of expertise in regional anesthesia is needed when treating infants due to their unique development.