Background: Tissue defects of the trunk and limbs after oncologic surgery and radiation require plastic reconstructive tissue coverage. Depending on the location and size of the wound as well as the interdisciplinary treatment concept, different reconstructive procedures are performed. These range from skin transplantation to local and pedicle flaps, to perforator flaps and free microsurgical tissue transfer. Methods: The modern “reconstructive ladder” can be regarded as an orientation for the sequence of the reconstructive options. Considering the patient’s wishes and risk profile, an individual reconstructive concept must be devised. The best functional and simultaneously safest procedure with the smallest secondary defect is to be chosen. Wound preconditioning via vacuum-assisted closure can precede definitive tissue coverage in order to optimize local conditions. Conclusion: Safe tissue coverage can be achieved even in advanced stages of oncologic disease and after extensive surgery by performing wound preconditioning and arteriovenous loop grafting to induce safe de novo recipient vessels for two-stage free tissue transfer. The choice between maximum plastic reconstructive options for a curative approach or limited palliative surgery is to be harmonized and balanced with therapeutic goals and the patient’s biologic resources. Preservation and restoration of quality of life and functionality is the plastic surgeon’s dictum.