Iodine and its antibacterial properties have been used for the prevention or management of wound infections for over 150 years. However, the use of solutions (tincture) of iodine has been replaced by the widespread use of povidone–iodine, a water-soluble compound, which is a combination of molecular iodine and polyvinylpyrrolidone. The resultant broad spectrum of antimicrobial activity is well documented and its efficacy, particularly in relation to resistant micro-organisms such as methicillin-resistant Staphylococcus aureus, has been shown. In the clinical environment, there is no general agreement regarding the ‘best’ antiseptic and the practice varies widely. This article reviews the studies that have assessed the efficacy of povidone–iodine in hand disinfection and skin preparation and its use as an antiseptic irrigant. Although there is a distinct lack of well-designed, randomised controlled trials evaluating antiseptic efficacy, selection should be based on the next best available evidence. This evidence suggests that the use of povidone–iodine as an agent of choice is dependent on the clinical need but is also likely to be influenced by personal preference.