For more than 150 years, iodine has been used for the prevention of infection and for the treatment of wounds. Nowadays a large amount of published evidence is available and, although it is generally in support of the use of iodine product, it is confused by being a mixture of laboratory, animals and human studies, often using different preparations. This makes interpretation and comparison difficult. After new developments and publications, the role of iodine in antisepsis and in wound management needs to be reevaluated. We mainly focused our review on the following problems: the role of the newly developed formulations of iodine preparations, its antimicrobial activity, the possibility of impairing the wound healing process, the role of iodine in the problem of growing resistance against antibiotics and antiseptics. New formulations seem to keep the same clinical efficacy, avoiding the problem of toxicity; it seems that the antibacterial activity of iodine is superior compared to other products and, in contrast with antibiotics and other antiseptics, it seems to have no resistance problem. It seems that povidone-iodine has all the characteristics to become the first choice antiseptic in wound treatment.