The capsaicin receptor TRPV1 is an emerging target for the treatment of pain with a unique expression profile in peripheral nociceptors and the ability to show polymodal activation, TRPV1 is an important integrator of responses to inflammatory mediators. Sensitization of TRPV1 during chronic pain is believed to contribute to the transduction of noxious signaling for normally innocuous stimuli and consequently the search for novel TRPV1 therapeutics is intense. The current understanding of the physiological role the receptor, as well as the potential therapeutic utility and emerging liabilities of TRPV1 modulators are discussed.