Transient receptor potential melastatin 8 (TRPM8) was originally cloned from prostate tissue. Shortly thereafter, the protein was identified as a cold- and menthol-activated ion channel in peripheral sensory neurons, where it plays a critical role in cold temperature detection. In this chapter, we review our current understanding of the molecular and biophysical properties, the pharmacology, and the modulation by signaling molecules of this TRP channel. Finally, we examine the physiological role of TRPM8 and its emerging link to various human diseases, including pain, prostate cancer, dry eye disease, and metabolic disorders.