Antibiotic recommendations for treating skin infections have been published many times in the past 30 years. Prior to 2000, the recommendations focused on the use of β-lactam antibiotics, such as cephalosporins, amoxicillin-clavulanate, or β-lactamase stable penicillins. These agents are still recommended, and used, for wild-type methicillin-susceptible strains of Staphylococcus spp. However, since the mid-2000s there has been an increase in methicillin-resistant Staphylococcus spp (MRSP). The increase among S pseudintermedius in animals coincided with the increase in methicillin-resistant S aureus that was observed in people near the same time. This increase led veterinarians to reevaluate their approach to treating skin infections, particularly in dogs. Prior antibiotic exposure and hospitalization are identified as risk factors for MRSP. Topical treatments are more often used to treat these infections. Culture and susceptibility testing is performed more often, especially in refractory cases, to identify MRSP. If resistant strains are identified, veterinarians may have to rely on antibiotics that were previously used uncommonly for skin infections, such as chloramphenicol, aminoglycosides, tetracyclines, and human-label antibiotics such as rifampin and linezolid. These drugs carry risks and uncertainties that must be considered before they are routinely prescribed. This article will discuss these concerns and provide veterinarians guidance on the treatment of these skin infections.