The choice of treatment for MRSA infections is based on the type and severity of infection. There are simple infections caused by MRSA like cellulitis, boils, and abscesses. More complicated infections caused by MRSA include pneumonia, joint infections, sepsis (overwhelming bacteria in the blood), and necrotizing fasciitis. Making the choice on how to treat the infection is based on a few simple decisions: is it life-or limb-threatening, and how likely is it to be MRSA? Observation works when the infection is localized and is unlikely to be MRSA; treatment would include waiting, watching, and washing the infection with soap and water. Some types of antibiotics can be used to treat MRSA infections. Surgery is another option when treating more serious cases of MRSA. Doctors have to be careful about making the right treatment choice because making the wrong choice could cause a not-so-sick patient to become very sick in a short period of time.

The most common way to treat MRSA infections is by using antibiotics. Penicillin was given to the first patient in 1941, and the first report of S aureus resistance to penicillin was in 1942. Some common antibiotics used to treat MRSA are sulfa drugs (TMP-SMX; +/- combination with rifampin), minocycline, doxycycline, moxifloxacin, levofloxacin, and clindamycin, and are used to treat "out patients" (non-hospitalized patients). For more seriously ill patients ("in patients"), doctors typically use the antibiotics vancomycin and linezolid, which are given through an intravenous line. Antibiotics destroy or prevent bacteria from multiplying. Antibiotics are not effective when a resistant strain emerges. The success rate of most antibiotics that are active or effective against MRSA is about 80-90%.

Another option when treating MRSA infections is surgery. Simple surgery is reserved for treating localized abscess like releasing pus (making cut in the skin to open a boil or abscess). More complicated surgery is for the truly sick patients who have serious infections in the joint or lung or necrotizing fasciitis. Surgery would include removing a large portion of skin or tissues or even amputation (removing a limb). Surgery is usually combined with antibiotics and sometimes needs to be repeated. It could cost tens or hundreds of thousands of dollars to have these surgeries. Most people who have surgery for MRSA infections are very sick and are usually in the intensive care unit.