: The treatment of pain, both acute and chronic, has been a focus of medicine for generations. Physicians have tried to develop novel ways to effectively manage pain in surgical and post-surgical settings. One intervention demonstrating efficacy is nerve blocks. Single-injection peripheral nerve blocks (PNBs) are usually preferred over continuous PNBs, since they are not associated with longer lengths of stay. The challenge of single injection PNBs is their length of duration, which at present is a major limitation. Novel preparations of local anesthetics have also been studied, and these new preparations could allow for extended duration of action of anesthetics. An emerging preparation of bupivacaine, exparel, uses a multivesicular liposomal delivery system which releases medication in a steady, controlled manner. Another extended-release local anesthetic, HTX-011, consists of a combination of bupivacaine and low-dose meloxicam. Tetrodotoxin, a naturally occurring reversible site 1 sodium channel toxin derived from pufferfish and shellfish, has shown the potential to block conduction of isolated nerves. Neosaxitoxin is a more potent reversible site 1 sodium channel toxin also found in shellfish that can also block nerve conduction. These novel formulations show great promise in terms of the ability to prolong the duration of single injection PNBs. This field is still currently in development, and more researchers will need to be done to ensure the efficacy and safety of these novel formulations. These formulations could be the future of pain management if ongoing research continues to prove positive effects and low side effect profiles.