The identification of compounds that can effectively and safely treat chronic pain is a major challenge of biomedical research. One approach is to optimize currently active analgesic treatments, notably by reducing their side effects. An example of this approach is the recent development of a novel class of nonsteroidal antiinflammatory drugs (NSAIDs), the cyclo-oxygenase 2 inhibitors, that lack the limiting gastrointestinal side effects of the traditional NSAIDs. Another approach, based on the recent development of molecular biology, is to develop analgesic compounds acting on new targets. These include notably ion channel blockers (TTX-resistant sodium channel blockers specific for nociceptors, N-type calcium channel blockers), nicotine receptor agonists, peptide receptor antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists, vanilloids, new opioid compounds, cannabinoids, selective alpha2-adrergic agonists, purinergic modulators. Most of these compounds are currently in preclinical or early clinical investigation. However, the development of more predictable in vitro and in vivo tests and the broadening use of clinical models of experimental pain, will hopefully help increase the proportion of drugs that will become successful analgesics in clinical practice.