Varenicline (VCL) is a modulator of nicotinic acetylcholine receptors (nAChRs) that acts as a partial agonist at α4β2 and α6β2 nAChRs and a full agonist at homomeric α7 nAChRs; VCL may also display agonist activity at β4 nAChR subunits. This compound displays neuromodulatory, cognition enhancing, analgesic, and reward and reinforcement modulating activities. VCL is clinically used as a smoking cessation therapy and is currently under examination as a treatment to decrease alcohol consumption as well. Like other nicotinic agonists, VCL exhibits some cognitive benefit, enhancing working memory in primate models. This compound also induces an analgesic effect in animal models of chronic pain undergoing the formalin test.