OBJECTIVE Global brachial plexus lesions with multiple root avulsions are among the most severe nerve injuries, leading to lifelong disability. Fortunately, in most cases primary and secondary reconstructions provide a stable shoulder and restore sufficient arm function. Restoration of biological hand function, however, remains a reconstructive goal that is difficult to reach. The recently introduced concept of bionic reconstruction overcomes biological limitations of classic reconstructive surgery to restore hand function by combining selective nerve and muscle transfers with elective amputation of the functionless hand and its replacement with a prosthetic device. The authors present their treatment algorithm for bionic hand reconstruction and report on the management and long-term functional outcomes of patients with global brachial plexopathies who have undergone this innovative treatment. METHODS Thirty-four patients with posttraumatic global brachial plexopathies leading to loss of hand function consulted the Center for Advanced Restoration of Extremity Function between 2011 and 2015. Of these patients, 16 (47%) qualified for bionic reconstruction due to lack of treatment alternatives. The treatment algorithm included progressive steps with the intent of improving the biotechnological interface to allow optimal prosthetic hand replacement. In 5 patients, final functional outcome measurements were obtained with the Action Arm Research Test (ARAT), the Southampton Hand Assessment Procedure (SHAP), and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. RESULTS In all 5 patients who completed functional assessments, partial hand function was restored with bionic reconstruction. ARAT scores improved from 3.4 ± 4.3 to 25.4 ± 12.7 (p = 0.043; mean ± SD) and SHAP scores improved from 10.0 ± 1.6 to 55 ± 19.7 (p = 0.042). DASH scores decreased from 57.9 ± 20.6 to 32 ± 28.6 (p = 0.042), indicating decreased disability. CONCLUSIONS The authors present an algorithm for bionic reconstruction leading to useful hand function in patients who lack biological treatment alternatives for a stiff, functionless, and insensate hand resulting from global brachial plexopathies.