Root avulsions due to traction to the brachial plexus causes complete and permanent loss of function. Until fairly recent, such lesions were considered impossible to repair. Here we review clinical repair strategies and current progress in experimental ventral root avulsion lesions. The current gold standard in patients with a root avulsion is nerve transfer, whereas reimplantation of the avulsed root into the spinal cord has been performed in a limited number of cases. These neurosurgical repair strategies have significant benefit for the patient but functional recovery remains incomplete. Developing new ways to improve the functional outcome of neurosurgical repair is therefore essential. In the laboratory, the molecular and cellular changes following ventral root avulsion and the efficacy of intervention strategies have been studied at the level of spinal motoneurons, the ventral spinal root and peripheral nerve, and the skeletal muscle. We present an overview of cell-based pharmacological and neurotrophic factor treatment approaches that have been applied in combination with surgical reimplantation. These interventions all demonstrate neuroprotective effects on avulsed motoneurons, often accompanied with various degrees of axonal regeneration. However, effects on survival are usually transient and robust axon regeneration over long distances has as yet not been achieved. Key future areas of research include finding ways to further extend the post-lesion survival period of motoneurons, the identification of neuron-intrinsic factors which can promote persistent and long-distance axon regeneration, and finally prolonging the pro-regenerative state of Schwann cells in the distal nerve.