Nociception is the process of transmission of painful signals by nociceptors in the primary afferent nerve fibers, which specifically respond to noxious stimuli. These noxious stimuli are detected by nociceptors and converted into electrical signals, which are then transmitted to the spinal cord, thalamus, and the cerebral cortex, where pain is finally sensed. Transient receptor potential (TRP) ion channels have emerged as a family of evolutionarily conserved ligand-gated ion channels that function as molecular detectors of physical stimuli. Several member of this family, at least six channels from three TRP family subtypes (TRPV1–4, TRPM8, and TRPA1), are expressed in nociceptors, where they act as transducers for signals from thermal, chemical, and mechanical stimuli and play crucial roles in the generation and development of pathological pain perception. This review focuses on the increasing evidence of TRP channel involvement and contribution in nociceptive pain and the pain hypersensitivity associated with peripheral inflammation or neuropathy, and on the renewed interest in targeting TRP channels for pain relief.