Antibiotic-resistant bacteria continue to be a major health concern worldwide. In particular, Staphylococcus aureus, both methicillin-resistant and -sensitive, are of concern in their ability to cause difficult skin and underlying tissue infections. Melaleuca alternifolia oil (tea tree oil), an essential oil, has demonstrated promising efficacy in treating these infections. Tea tree oil has been used for centuries as a botanical medicine, and has only in recent decades surfaced in the scientific literature as a promising adjunctive wound treatment. Tea tree oil is antimicrobial, anti-inflammatory, and has demonstrated ability to activate monocytes. There are few apparent side effects to using tea tree oil topically in low concentrations, with contact dermatitis being the most common. Tea tree oil has been effective as an adjunctive therapy in treating osteomyelitis and infected chronic wounds in case studies and small clinical trials. There is a need for larger clinical trials to further examine efficacy of tea tree oil as an adjunctive wound therapy, as well as improved guidelines for developing plant-based medicines.