The neuromuscular junction is a well-characterized point of vulnerability in aging skeletal muscle. The first study documenting neuromuscular junction morphological alterations in aged rodents was published in 1966 [1] with dozens of rodent studies since, and this has been corroborated in aging humans [2]. Although much of the morphological alterations to the neuromuscular junction with aging reflect a remarkable plasticity of this structure in helping to preserve the fidelity of the motoneuron:muscle fiber communication for most of the adult lifespan, evidence suggests that this plasticity is finite. Specifically, there is evidence for failed reinnervation in advanced age that leads to an accumulation of persistently denervated muscle fibers that are a major driver of accelerated muscle atrophy and weakness. Underscoring this point, our previous studies highlight that denervated muscle fibers in aging muscle are markedly atrophied, whereas innervated muscle fibers in aged muscle are only mildly atrophied compared to those from young adult muscle. On the other hand, a maintenance of reinnervation is characteristic of atrophy-resistance with aging, as is seen when comparing muscles with varying atrophy susceptibility within the same organism. In addition, superior reinnervation capacity is a feature of aging humans who are better able to maintain muscle mass (e.g., Masters track and field athletes). In this latter respect, although exercise itself likely contributes to better preservation of muscle innervation in advanced age (e.g., by preserving mitochondrial function), muscle proteomics analysis finds that at least some features of skeletal muscle in highly functioning elderly have not been previously identified as exercise-responsive, implicating a genetic and/or gene x environment interaction. Greater understanding of the mechanisms responsible for modulating reinnervation capacity and severity of aging muscle atrophy will be an important key to identifying strategies for better maintaining mobility with aging.