Transient receptor potential vanilloid subtype 3 (TRPV3) is an ion channel with a sensory function that is most abundantly expressed in keratinocytes and peripheral neurons. TRPV3 plays a role in Ca2+homeostasis due to non-selective ionic conductivity and participates in signaling pathways associated with itch, dermatitis, hair growth, and skin regeneration. TRPV3 is a marker of pathological dysfunctions, and its expression is increased in conditions of injury and inflammation. There are also pathogenic mutant forms of the channel associated with genetic diseases. TRPV3 is considered as a potential therapeutic target of pain and itch, but there is a rather limited range of natural and synthetic ligands for this channel, most of which do not have high affinity and selectivity. In this review, we discuss the progress in the understanding of the evolution, structure, and pharmacology of TRPV3 in the context of the channel’s function in normal and pathological states.