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The prevalence of skin and soft tissue infections (SSTIs) has been increasing in the United States. These infections are associated with an increase in hospital admissions. Hospitalists play an increasingly important role in the management of these infections and need to use hospital resources efficiently and effectively. When available, observation units are useful for treating low-risk patients who do not require hospital admission. Imaging tools may help to exclude abscesses and necrotizing soft tissue infections; however, surgical exploration remains the principal means of diagnosing necrotizing soft tissue infections. The most common pathogens that cause SSTIs are streptococci and Staphylococcus aureus. Methicillin-resistant S aureus (MRSA) is a prevalent pathogen, and concerns are increasing regarding the unclear distinctions between community-acquired and hospital-acquired MRSA. Other less frequent pathogens that cause SSTIs include Enterococcus species, Escherichia coli, Klebsiella species, Enterobacter species, and Pseudomonas aeruginosa. Cephalexin and clindamycin are suitable options for infections caused by streptococcal species and methicillin-susceptible S aureus. The increasing resistance of S aureus and Streptococcus pyogenes to erythromycin limits its use in these infections, and better alternatives are available. Parenteral cefazolin, nafcillin, or oxacillin can be used in hospitalized patients with nonpurulent cellulitis caused by streptococci and methicillin-susceptible S aureus. When oral MRSA therapy is indicated, clindamycin, doxycycline, trimethoprim-sulfamethoxazole, or linezolid is appropriate. Vancomycin, linezolid, daptomycin, tigecycline, telavancin, and ceftaroline fosamil are intravenous options that should be used in MRSA infections that require patient hospitalization. In the treatment of patients with SSTIs, hospitalists are at the forefront of providing proper patient care that reduces hospital costs, duration of therapy, and therapeutic failures. This review updates guidelines on the management of SSTIs with a focus on infections caused by S aureus, particularly MRSA, and outlines the role of the hospitalist in the effective management of SSTIs.