Acute Bacterial Skin and Soft Tissue Infections, abbreviated SSTIs, are commonly encountered in the outpatient setting. Understanding the nuances of these infections will ensure appropriate therapy and end microbial management. Guidelines for the management of SSTIs were updated in 2014, to simplify the management algorithm for SSTI, and also to account for increased prevalence of Methicillin-resistant Staphylococcus Aureus, abbreviated MRSA, as a causative agent of community onset infections. In the management of SSTIs, the first critical decision node requires the clinician to identify an infection as non-purulent or purulent, as these descriptive clinical categories denote different likely etiologies and different therapeutic approaches. Necrotizing infections, cellulitis and erysipelas, a type of cellulitus that is characterized by the presence of a well-defined and often red border, are counted among the non-purulent SSTIs. The category of purulent SSTIs includes furuncles, carbuncles and abcesses. Following the determination of purulent verse non-purulent, the clinician must categorize the infection as severe, moderate or mild with these designations dictating appropriate clinical therapy. Mild non-purulent SSTIs, which are often encountered in the outpatient setting, can be treated with oral antibiotics. Beta-hemolytic streptococci, account for the majority of infections and therefore dictate which agents can be used for empiric coverage. As a consequence, most outpatients with non-purulent Cellulitus or Erysipelas can be treated with an orally administered penicillin or cephalosporin, or if penicillin allergic, clindamycin can be used as an alternative. While it is generally believed that trimethoprim-sulfamethoxazole lacks activity against beta-hemolytic streptococci, recent evidence suggests that this may be incorrect. A clinical trial comparing clindamycin to trimethoprim-sulfamethoxazole for the management of mild skin infections, did not show any difference in cure rates between these two medications. The use of rifampin, either as a single agent or in combination, is not recommended. The recommended duration of therapy is five days, although discontinuation of therapy is ultimately dictated by the clinical response. Patients identified as having a moderate non-purulent SSTI, may require intravenous antibiotics. Again, penicillins or cephalosporins provide excellent coverage. An infection is categorized as moderate in contrast to simple if the patient has a typical Cellulitus accompanied by systemic signs of infection, which may include a temperature greater than 38 degrees celsius, a heart rate greater than 90 beats per minute, a respiratory rate greater than 24 breaths per minute and an abnormal white blood cell count, either elevated greater than 12 thousand or depressed less than 400 cells per microliter. Recurrent episodes of cellulitus should prompt investigation for predisposing conditions in the affected area including edema, obesity, eczema, venous insufficiency and other co-infections for example tinea pedis. Prophylaxis may be considered for patients experiencing three to four episodes per year despite mitigation efforts. Any patient diagnosed with a severe non-purulent cellulitus, requires emergent inpatient evaluation and management with surgical debridement to define the extent of infection, and empiric antimicrobial therapy to stop the spread. In such cases, broad-spectrum empiric therapy is necessary, including anti MRSA gram positive coverage and anti-pseudomonas gram-negative, plus anaerobic coverage. Culture should be sent from any surgical exploration to determine primary etiology, monomicrobial versus polymicrobial which will ultimately dictate targeted therapy. The primary treatment for any level of purulent SSTI is incision and drainage. If lumps bumps or pus are present, the infection is most likely due to staph aureus and at least in the US is most likely to be resistant to beta-lactams. The primary treatment of a cutaneous abscess is incision and drainage, with antibiotics often being unnecessary. Certain criteria merit the addition of antimicrobial therapy following I and D, including severe or extensive disease, for example involving multiple sites of infection. Signs and symptoms of systemic illness: impaired host defenses, extremes of age, lack of clinical improvement following incision and drainage. This may occur for example, in abscesses in difficult to drain areas for example the face, hands or genitalia. Patients with moderate disease may be managed with oral antibiotics following I and D. Options for empiric coverage include Trimethoprim-sulfamethoxazole and Doxycycline. These choices can be modified to match culture and sensitivity data from the I and D specimen. Empiric options for severe infections include the parenteral agents, vancomycin, daptomycin, linezolidit, televacin and ceftaroline among others. These options can be de-escalated to appropriate parenteral MSSA coverage if culture results allow. Cost may be an important consideration for your institution and should be considered on a case by case basis depending on individual pharmacy contracts. In general, older agents for which a generic is available, are typically cheaper and may offer a comparable spectrum of coverage to other brand name agents. Immunocompromised patients with skin and soft tissue infections are almost always classified as severe, owing to their underlying immune defects. It should also be noted that these patients may have skin infections from unusual organisms and the clinician should maintain a high level of suspicion for these including fungi.