Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are developing as a prominent public-health threat. While minor CA-MRSA infections are treatable in an out-patient setting, the pharmacotherapeutic options for oral therapies are dwindling as resistance continues to rise in general and levels of susceptibility vary geographically. In many instances, fluoroquinolones and clindamycin are not reasonable empiric treatment choices, leaving physicians with trimethoprim-sulfamethoxazole, doxycycline or linezolid as viable options, depending on patient-specific circumstances and the impact of potential adverse effects. Resistance to intravenous options remains low and attention should be focused on the site and severity of infection when choosing antibiotic/intravenous immunoglobulin treatment. Clinical trials directly comparing antibiotic options in both out-patient and in-patient settings are needed to enhance recommendations for empiric therapy algorithms.