Transient receptor potential (TRP) channels belong to a varied superfamily of membrane proteins with multiple functions. Most TRP channels are permeable to Ca2+ ions and are thus involved in physiological processes related to Ca2+-mediated homeostasis and signaling. Every year, thousands of research articles are published describing new roles for TRP channels, both in normal and pathological physiological conditions. This functional diversity probably stems from the presence of various structural motifs in each one of its members, some of which have been identified and characterized, at least at the level of their primary sequence (Latorre et al., 2009). Among this tremendous diversity, a few TRP channels are the only ion channels that have been unequivocally characterized as being directly gated by changes in temperature (Islas and Qin, 2014). These are generically grouped into the category of thermoTRP channels and include channels that are gated by cold or hot temperatures. The following members of three subfamilies of TRP channels are recognized as thermoTRPs: TRPA1, TRPM2, TRPM8, and TRPV1–4. These channels and their mechanisms of gating will be the focus of the present chapter. These key proteins provide the molecular substrate for the detection of temperature and temperature changes (Islas and Qin, 2014), in organisms as varied as worms (Chatzigeorgiou et al., 2010) and humans (Gavva, 2008; Gavva et al., 2008) and play important roles in pain, inflammation, and other physiological processes.