Surgical site infections (SSI) remain a significant problem to both the patients and the healthcare system. Value care and standardized quality measures continue to promote improvement in surgical asepsis, but certain debates remain unresolved in the field of surgical hand antisepsis.Review of relevant accounts and literature.Controversy has existed regarding the U.S. Food and Drug Administration (FDA)'s 1994 Tentative Final Monograph (TFM), which defined how surgical hand antisepsis products are assessed. Issues involving neutralizers and demonstration of a cumulative effect were addressed in the FDA's Proposed Rule in 2015. Few studies have used SSI as a primary outcome and instead have used a surrogate marker (colony-forming units [CFU]). Quantitative microbiology studies suggest a minimum bacterial inoculum of 105-107 CFU/mL is necessary to cause a clinical infection. Outcomes of antisepsis likely are driven by both active ingredient(s) and overall product formulation. Povidone-iodine aqueous scrubs are inferior to chlorhexidine gluconate (CHG) 4% aqueous scrubs and alcohol-based rubs (ABR). The SSI and CFU outcomes studies support the equivalence or superiority of ABR over CHG.Both ABRs and CHG 4% are preferred to povidone-iodine for surgical hand antisepsis. Well-powered randomized controlled trials measuring SSI as a primary outcome, as well as those designed according to either TFM or European methodology, with appropriate controls and neutralizers, are warranted. These trials should incorporate different ABR formulations and CHG 4%, as well as skin tolerance assessments and a cost analysis.