The past few years have witnessed a remarkable progress in understanding the neurobiology of pain. Important advances have been made particularly in the field of peripheral signal transduction in nociceptors. Membrane receptors have been identified for capsaicin, a pungent ingredient of chilli peppers, protons (i.e. acidic solutions) and for heat, three stimuli that specifically excite nociceptors. Of particular interest appears to be the first cloned capsaicin receptor, VR1, which has been suggested to serve as an integrator of these three nociceptive stimuli. These findings not only give new insights into the molecular machinery of nociceptor activation and sensitization, but can also provide a rational basis for pharmacological research aiming for a new class of peripherally acting analgesics, which should selectively interfere with nociceptor activation.