Our knowledge and understanding of the pathophysiology and treatment of pain is increasing; however, we should not lose sight of the simple opportunities that exist for intercepting pain at peripheral targets. Although systemic medication often has peripheral and central modes of action, the appeal for provision of medication close to where these peripheral targets exist should be high. If these sites can be attacked with relatively high concentrations of active drug while keeping systemic levels of that drug below the level at which systemic side effects become apparent, then this should lead to desirable outcomes. Even though the number of true topical agents with an indication for this use is small, a number of other topical agents are available that evidence suggests have the possibility of being effective. Given the increased understanding of pain, the likelihood of further topical agents becoming available is high.