In addition to the generic properties of honey, manuka honey has a nonperoxide antimicrobial activity largely attributed to methylglyoxal. Commercially, manuka honey is graded against a standard antiseptic, phenol, to provide a measure of antimicrobial activity referred to as the unique manuka factor (UMF). The higher the UMF, the greater the antimicrobial activity. However, more recently, there is evidence that manuka honey can also modulate the initial inflammatory response through activation of toll-like receptor 4 on monocytes to enhance production of cytokines important in tissue repair and regeneration. Recent studies investigating the effects of manuka honey on second intention healing of lower limb wounds in horses have shown that wounds treated with UMF 20 manuka honey retracted less and healed faster than untreated wounds. Using this wound healing model, the primary effects of manuka honey appeared to be associated with the modulation of the initial inflammatory reaction rather than its antimicrobial effects. Based on the current knowledge, treatment with manuka honey should be instituted as soon as possible after injury. Where bacterial contamination is substantial, manuka honey with a UMF ≥15 should be used. While bandages will improve the contact between the honey and the wound and may be indicated in the early stages of wound healing, prolonged bandaging may lead to the production of excessive granulation tissue. If topical treatment without a bandage is to be used, more honey is not necessarily better. Using a thin film combined with regular application, contact times may be optimised. Application 2–3 times daily to open wounds may improve efficacy. Manuka honey should be applied for at least 21 days after wounding but there may be beneficial effects if it is applied until wound healing is almost complete.