: Isolated peripheral motor dysfunction due to lower motor neuron or peripheral nerve disorders presents an interesting challenge to clinicians because of the diverse differential diagnosis with a broad range of prognoses. : We retrospectively reviewed clinical data of adults who presented over 12 years with muscle weakness, atrophy, or fasciculations, but without hyperreflexia or sensory involvement. : In 119 patients, 52% had a motor neuron disease (MND), 13% had immune neuropathies, 11% had genetic neuronopathies, 10% had residual or post-polio syndrome, 5% had benign fasciculation, 1% had an infectious etiology, and 8% were not given a final diagnosis. Only MND patients had cognitive dysfunction or frontal release signs. Bulbar and respiratory symptoms virtually excluded consideration of immune neuropathy. : Only half of the patients were diagnosed with MND. A significant minority have treatable conditions. Cognitive involvement, frontal release signs, and bulbar or respiratory symptoms are strongly suggestive of MND.