Local anesthetics form the backbone of pain control techniques in dentistry. Used properly, local anesthetics are the safest and most effective drugs for the prevention and management of peri- and post-operative pain. This Quality Resource Guide (QRG) provides an evidence-based review of the evolution and clinical characteristics of local anesthetic solutions available in North America and discusses their differences in metabolism. An in-depth discussion of local anesthetic systemic toxicity (LAST), its prevention, recognition and management provide guidance that should be periodically reviewed by all dental practitioners. Recent advances in local anesthetics, including articaine, the use of buffering solutions and the role of phentolamine in reversing local anesthesia are thoroughly assessed. The QRG will serve as an important update resource for practitioners administering local anesthetics and a useful periodic review.