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The reconstruction of complex soft tissue losses associated with underlying fractures remains a clinical challenge. Many different factors have to be considered in the treatment algorithm to achieve functional recovery of the limb. Timing between injury and the definitive reconstruction has become less important. Instead the focus needs to be on aggressive debridement combined with a targeted antibiotic therapy and negative pressure wound therapy treatment to bridge the time until the optimal setup both on patient and clinician site is available. Defect coverage can often be achieved with regional flaps in the upper part of the lower limb. The distal third of the lower limb often requires coverage with a free tissue transfer. The current literature offers no evidence to support superior outcomes of either limb salvage or primary amputation for type IIIB and IIIC tibial fractures. When outcomes are similar between two treatment strategies, economic analysis that incorporates cost and preference may define an optimal treatment strategy to guide physicians and patients.