Capsaicin, the most pungent ingredient in red peppers, has been used for centuries to remedy pain. Recently, its role has come under reinvestigation due to evidence that the drug acts selectively on a subpopulation of primary sensory neurons with a nociceptive function. These neurons, besides generating pain sensations, participate through an antidromic activation in the process known as neurogenic inflammation. The first exposure to capsaicin intensely activates these neurons in both senses (orthodromic: pain sensation; antidromic: local reddening, oedema etc.). After the first exposure, the neurons become insensitive to all further stimulation (including capsaicin itself). This evidence led to the proposal of capsaicin as a prototype of an agent producing selective analgesia. This perspective is radically different from previous 'folk medicine' cures, where the drug was used as a counter-irritating agent (i.e. for muscular pain). The new concept requires that capsaicin be repeatedly applied on the painful area to obtain the desensitisation of the sensory neurons. Following this idea, capsaicin has been used successfully in controlling pain in postherpetic neuralgia, diabetic neuropathy and other conditions of neuropathic pain. Furthermore, evidence indicates that capsaicin could also control the pain of osteoarthritis. Finally, repeated applications of the drug to the nasal mucosa result in the prevention of cluster headache attacks. On the basis of this evidence, capsaicin appears to be a promising prototype for obtaining selective analgesia in localised pain syndromes.