The TRPV1 vanilloid receptor, first cloned and characterized in 1997, is a non selective cation channel expressed in primary sensory neurons, and is a key pain sensor and integrator. Activators of this receptor are varied and include capsaicin, the pungent phenolic principle from hot chilli peppers, endogenous lipid anandamide, noxious heat, and low extracellular pH. Agonists of the TRPV1 receptor have been investigated for development due to their analgesic effect that results from the receptor desensitization. However, all agonists including capsaicin cause initial burning effect, and have the potential for other undesirable effects, which complicates effective therapy. The development of animal pain models involving TRPV1 receptor blockade through small molecules and characterization of TRPV1 knockout mice models in recent years has provided a compelling argument in favor of pursuing the development of selective TRPV1 antagonists as novel analgesic agents. This article will provide an overview of the various chemical classes of agonists and antagonists of TRPV1 receptor along with their therapeutic potential and possible side effects.