The intra‐operative control of pain and hemorrhage represents significant factors that are required for modern, effective, and efficient endodontic surgical procedures. This review focuses on these important issues and emphasizes the level of clinical evidence of various studies reporting on interventions to alter pain or hemorrhage. To accomplish this goal, the review will provide an overview of the fundamental properties of local anesthetics and hemostasis and then build upon this foundation to provide evidence‐based recommendations for treatment considerations.