Objectives: The aim of this study is to review the available literature addressing the safety and efficacy of antiseptics in surgical wounds. The different antiseptic solutions, irrigation volumes, time scales and delivery methods have been compared so that evidence-based recommendations on antiseptic use in plastic, orthopaedic, foot and ankle surgical procedures can be proposed. Methods: A literature search was performed using the online databases Medline and EMBase to identify in-vitro and in-vivo studies pertaining to antiseptic use in an orthopaedic context. Terms including antiseptic, irrigation fluid, bacitracin, hydrogen peroxide, povidone-iodine and chlorhexidine were searched. Literature published in English from inception to July 2020 in which the full text was accessible was considered for inclusion. Cellular and animal studies were included on the basis that authors analysed antiseptic efficacy and/or toxic effect of antiseptic on cells present in orthopaedic wounds. Clinical studies that met the criteria for inclusion in this review assessed antiseptic use in a surgical context, with a focus on foot and ankle procedures. These included case reports, case series, case control, prospective and retrospective studies as well as randomised controlled trials. Studies were categorised as in-vitro, animal and human studies. Twenty-three, eleven and forty-seven studies were identified as in-vitro, animal and human studies respectively. These have been summarised and presented herein in a narrative format. Results: There is strong evidence that skin preparation with antiseptics before plastic and orthopaedic procedures reduces the risk of post-operative infection. Conclusion: Routine prophylactic intra-operative antiseptic use should be performed with caution as they increase the risk of local and systemic complications. However, there is strong evidence supporting the use of antiseptics pre-operatively when preparing the skin. Determining the best antiseptic preparation remains a matter of debate since a single agent or solution is not effective against all organisms. Further research is therefore needed to assess the efficacy of antiseptics in prevention and treatment of infections.