We feel a wide range of temperatures spanning from cold to heat. Within this range, temperatures over about 43 degrees C and below about 15 degrees C evoke not only a thermal sensation, but also a feeling of pain. In mammals, six thermosensitive ion channels have been reported, all of which belong to the TRP (transient receptor potential) super family. These include TRPV1 (VR1), TRPV2 (VRL-1), TRPV3, TRPV4, TRPM8 (CMR1), and TRPA1 (ANKTM1). These channels exhibit distinct thermal activation thresholds (>43 degrees C for TRPV1, >52 degrees C for TRPV2, >32-39 degrees C for TRPV3, >27-35 degrees C for TRPV4, <25-28 degrees C for TRPM8, and <17 degrees C for TRPA1) and are expressed in primary sensory neurons as well as other tissues. The involvement of TRPV1 in thermal nociception has been demonstrated by multiple methods, including the analysis of TRPV1-deficient mice. Temperature thresholds for activation of TRPV1, TRPV4, and TRPM8 are not fixed but changeable. Reduction of the temperature threshold for TRPV1 activation is thought to be one mechanism of inflammatory pain. Significant advances in thermosensation research have been made in the last several years with the cloning and characterization of thermosensitive TRP channels. With these clones in hand, we can begin to understand thermosensation from a molecular standpoint.