Clinical pulpal anesthesia is dependent on the interaction of three major factors. (1) the dentist (2) the patient and (3) local anesthesia. Many patients fear endodontic treatment due to a concern about pain. Although pain treatment is well managed in many endodontic patients, there exists a group of patients who do not receive adequate local anesthesia. The purpose of this review article is to discuss the possible reasons for pulpal anesthetic failures and also to focus on the measures for developing effective approaches for the same.