The 2021 Nobel Prize in Physiology or Medicine is awarded to American physiologist David Julius and molecular biologist Ardem Patapoutian for their groundbreaking discoveries of receptors for temperature and touch. The ability to perceive external stimuli, such as hot and cold sensation and mechanical pressure, is crucial to our adaptation to the ever-changing environment, protecting us from harm. Prior to the discoveries of this year’s laureates, how temperature and mechanical stimuli are perceived and converted into electrical pulses was unknown. Unveiling of the temperature receptor TRPV1 and the touch receptors PIEZOs led to a thorough understanding of this process, also revealing more members of the TRP receptor family and PIEZO receptor family, furthermore encouraging scientists to research on its mechanisms and functions, pointing towards innovative treatment methods for tackling pain at the root. This article summarizes the discovery process, structure and mechanisms of these two receptors and also introduces illnesses caused by receptor mutations, shining light on their role as potential targets for drug development.