Antiseptics, with a broader spectrum of antimicrobial efficacy, lower risk of antibiotic resistance development, and minimal collateral damage to host tissues, are important alternatives to control the bioburden in wounds. Povidone iodine (PVP-I), in use for several decades, has the broadest spectrum of activity, a persistent antimicrobial effect, an ability to penetrate biofilms, and a lack of acquired or cross-resistance. It demonstrates good skin tolerance and low cytotoxicity. However, some reports on PVP-I have raised concerns over allergy, ineffective penetration, and toxic effects on host cells. The majority of these concerns are based on in vitro or rodent wound studies with diverse study designs and outcomes; these results may not be directly applicable in the clinical reality in humans. In this paper, we discuss the efficacy and safety of PVP-I and outline its place in wound healing in Asia, based on an appraisal of recent literature and clinical practice across the region.