Local anesthetic (LA) drugs have a vast safety record when used in appropriate dosages and routes. However, they have the propensity to cause adverse reactions which can range from mild nonspecific symptoms to severe life-threatening systemic toxicity. Increased plasma levels due to inadvertent intravascular injection or use of high dose in normal anatomic site can lead to cardiac arrest in an otherwise healthy patient which can be refractory to standard resuscitative measures. Fortunately, local-anesthetic systemic toxicity (LAST) is rare and usually limited to mild nonspecific symptoms. This chapter covers the incidence, pathophysiology, signs and symptoms, management of last, theories of mechanism of le effectiveness in last, last in pediatric patients, and recent advances in the treatment of last. High index of suspicion should be maintained for LAST in any patient with altered mental status, seizure or cardiovascular symptoms following a regional blockade. Use of ultrasonography guidance for regional blocks has shown encouraging evidence in reduction in incidence of LAST and should be a rule rather than exception in years to follow.