Patients with complex upper extremity injuries represent a unique subset of the trauma population. In addition to extensive soft tissue defects affecting the skin, bone, muscles and tendons, or the neurovasculature in various combinations, there is usually concomitant involvement of other body areas and organ systems with the potential for systemic compromise due to the underlying mechanism of injury and resultant sequelae. In turn, this has a direct impact on the definitive reconstructive plan. Accurate assessment and expedient treatment is thus necessary to achieve optimal surgical outcomes with the primary goal of limb salvage and functional restoration. Nonetheless, the characteristics of these injuries places such patients at an increased risk of complications ranging from limb ischemia, recalcitrant infections, failure of bony union, intractable pain, and most devastatingly, limb amputation. In this article, the authors present an algorithmic approach toward complex injuries of the upper extremity with due consideration for the various reconstructive modalities and timing of definitive wound closure for the best possible clinical outcomes.