Local anesthetics are used with neuraxial and regional techniques to provide pain relief, most commonly postoperatively. Each agent is a sodium-channel blocker, although each agent differs in onset of action, potency, duration of action, and safety profile. Chemical structure and lipophilicity are the main determinants of these characteristics. The agents may be used alone or in combination with an additive which alters the local anesthetic’s properties . Clinically, local anesthetics provide pain relief in a multimodal approach. This reduces opiate consumption, opiate-related adverse effects, and length of stay. Additional benefits when using neuraxial techniques include decreases in mortality, venous thromboembolism, myocardial infarction, pneumonia, respiratory depression, and duration of ileus. Although there are many adverse effects, the most serious include neurologic and cardiovascular. Seizures and cardiac arrest may result from local anesthetic systemic toxicity when systemic levels are elevated or the patient is predisposed. Dose adjustment, removal, or reversal of the agent may be clinically indicated. Lipid emulsion therapy is a reversal agent which acts as a sequestering vehicle for the local anesthetic. Liposomal bupivacaine, the newest formulation of local anesthetic, may provide an increased duration of action compared with standard formulations, although more evidence is needed. This review contains 5 figures, 5 tables, and 59 references. Keywords: amide, ester, epidural, local anesthetic, local anesthetic systemic toxicity, lipid emulsion therapy, liposomal bupivacaine, peripheral nerve block