The purpose of preoperative surgical skin antisepsis is to decrease the number of microorganisms on the skin to the lowest possible number before the skin, the body’s first line of defense, is entered. Perioperative team members performing preoperative patient skin preparation should be aware of effective antiseptic products available for this purpose and how these products are selected for use in their organization. This educational activity will clarify US Food and Drug Administration (FDA) requirements for preoperative skin preparation drug products and discuss recent FDA Safety Communications. The differences between sterile and nonsterile antiseptic solutions will be described as well as issues related to sterilizing antiseptic solutions. An overview of the perioperative nurse’s role in influencing change and assuring the most effective antiseptic solutions are available for performing preoperative skin preparation will also be presented.