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Isolated neurological hand dysfunction including symptoms of weakness, numbness, clumsiness and dystonia are not uncommon complaints presenting to physicians in primary care as well as to neurologists, physiatrists, orthopedists and neurosurgeons. Etiologies of neurological hand dysfunction range from lesions of the central and peripheral nervous system pathways as well as the neuromuscular junction and muscle. In this article we present a series of four patients referred to a rural Physical Medicine & Rehabilitation presenting with similar symptoms of neurological hand dysfunction that ultimately had very different diagnoses. The goal of this article is to review the appropriate history, physical and examination findings and pertinent neuroanatomy needed to direct the clinician towards the workup needed to accurately diagnose and treat neurological hand dysfunction.