Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly becoming a major source of systemic infection in the community and healthcare settings. The disease is responsible for deaths among individuals without known risk factors and presents a therapeutic challenge for clinicians because of the bacteria’s complex epidemiology and mechanisms of antibiotic resistance. Furthermore, the skin and soft tissue are the most commonly infected organs. Consequently, it is necessary for the dermatologist to have an understanding of the management of the condition to prevent lethal manifestations and further spread to the community. This 4-part review covers the epidemiology, pathogenesis, and management of the disease, including new treatment options. The fourth part of the review will focus on additional therapeutic considerations in the management of MRSA infection.