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To summarize the current finding on SSTIs/ABSSSIs treatment duration.In 2013, the FDA approved the definition of acute bacterial skin and skin structure infections (ABSSSIs). From a clinical point of view, the new definition may present some advantages: the definition of the severity of the disease, the measurement of reduction in lesion size, and effectiveness of treatment primary endpoint at 48–72 h after treatment initiation. New therapeutic options with improved efficacy, safety, and/or pharmacodynamics are available for ABSSSIs and so far, several questions still need to be addressed for the management of these infections, including treatment duration.There is a wide variation of duration of antimicrobial treatment in skin and soft tissue infections. Plenty of published data available suggest that we should focus on the early response to shorten duration of treatment, and that the antimicrobial stewardship perspective is extremely helpful in underscoring the need for composite outcomes in clinical practice, as multiple tools are available to increase cost-efficacy, including reduction of treatment changes, early oral switch, early discharge (even from the Emergency Department), outpatient antimicrobial treatment, long-acting antibiotics, and all together, de-escalation treatment strategies.