Polihexanide is an antimicrobial compound suitable for clinical use in critically colonized or infected acute and chronic wounds. Its beneficial characteristic is attributable particularly to its broad antimicrobial spectrum, good cell and tissue tolerability, ability to bind to the organic matrix, low risk of contact sensitization, and wound healing promoting effect. In addition, no development of microorganism resistance during polihexanide use has been detected to date, nor does this risk appear imminent. The aim of therapy using polihexanide is to reduce the pathogen burden in a critically colonized or infected acute or chronic wound. An increasing number of articles on the subject of wound antisepsis with polihexanide can be found in the medical literature. However, there is still little published information on the practical use of polihexanide-containing wound antiseptics. The purpose of this review article is to describe the handling and the different possibilities of use of polihexanide-containing preparations, including the currently approved indications, contraindications and reservations. The use of polihexanide is not the only therapeutic option in management of wounds; therefore, priority is also given to prior surgical debridement and clarification of the cause of the underlying disease, including appropriate therapy.