Surgical-site infections (SSIs) are the most common healthcare-associated infections in patients undergoing surgery. Surgical site preparation to prevent SSI is aimed at reducing the number of microorganisms introduced into the operative sites. Antiseptics are used to remove transient bacteria and reduce the number of commensal organisms present on the skin. The most commonly used agents are chlorhexidine, povidone-iodine, and alcohol. All of these agents have broad-spectrum activity against various pathogens. Although each agent has its advantages and disadvantages, alcohol-based antiseptic solutions containing chlorhexidine are recommended in the available guidelines. Further well-designed studies are required to identify the best antiseptics for SSI prevention.