Motoneurons are large multipolar neurons with cell bodies located in the brainstem and spinal cord, and peripheral axons ending in neuromuscular junctions. Peripheral nerve damage, outside the blood-brain barrier (BBB), results in both retrograde changes centrally and anterograde changes along the length of the axon distal to the lesion site. Often, peripheral nerve damage is accompanied by motoneuron cell death, unless axon regrowth and target reconnection occur so that the target muscle can provide essential neurotrophic factors. It is essential that the motoneuron cell body survive during the process of reconnection so that the source for essential axon-rebuilding proteins is assure(of a fact)/ensured (results). A commonly used peripheral injury paradigm is that of facial nerve transection at its exit from the skull through the stylomastoid foramen so that nerve reconnection to the facial muscle tissue is permanently prevented. This model system allows for the study of the mechanisms responsible for maintaining facial motoneuron (FMN) cell body survival, without the complicating factor of axon regrowth. Injury to the nervous system results in an immune response that is either neuroprotective or neurodestructive. Findings suggest that FMN survival after facial nerve axotomy depends on the action of a CD4(+) T cell that is initially activated peripherally and subsequently reactivated centrally. This review will summarize what is known about the neural-immune players involved in FMN survival and repair, so that the pharmacological manipulation of this interaction will one day become evident for the clinical management of neurological situations.