The systematic developments of synthetically modified structures related to capsaicin known to have pungent properties found in chili peppers that could be useful as analgesic drug are described. It is found that identification of the receptor for capsaicin and the mechanism of its action greatly contributed to an understanding of the role transient receptor potential vanilloid subfamily 1 (TRPV1)-bearing nociceptors that might play an important role in various painful conditions.