TRPV1 and TRPA1 have traditionally been considered to function independently from each other as homomers, but their extensive co-expression in sensory neurons and recent evidence suggest that these channels can functionally interact and may form a complex as part of their normal function. Although TRPA1 and TRPV1 do not absolutely require interaction to maintain function in expression systems or even sensory neurons, their heteromerization may still result in dramatic effects on channel biophysical properties, pharmacology, signaling, regulation, and ultimately function. Understanding the regulation and functional significance of TRPA1-TRPV1 interaction is of tremendous clinical importance since first, both channels are the potential molecular targets for numerous therapeutic drugs; and second, TRPA1-TRPV1 co-expression is far more specific for nociceptive sensory neurons than expression patterns of TRPA1 or TRPV1 considered separately.