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Honey has been utilized for the treatment of wounds by ancient civilizations for millennia. In recent times, there has been renewed interest in the use of honey in the treatment of chronic wounds and burns in response to the increased development of antimicrobial resistance to antibiotics. The physical properties of honey enhance wound healing by increasing the release of oxygen from hemoglobin, inactivating bacterial proteases and drawing fluid out of the wound bed initiating autolytic debridement. Honey also has broad spectrum antimicrobial activity. Peroxide or non-peroxide bactericidal activity is derived from phytochemicals drawn from specific plant species. Of the honey varietals, manuka honey, from the manuka tree (Leptospermum scoparium) is the most widely studied for its non-peroxide antimicrobial properties and ability to improve wound healing. This review summarizes the known mechanisms of action of manuka honey and the results of 4 experimental studies performed by the authors using an equine model of second intention healing. In addition, the future direction of research investigating the use of different varietals of honey as a therapeutic agent to enhance wound healing is explored.