The diagnosis of peripheral neuropathy begins with determining whether the patient has peripheral nerve damage. The site of the lesion can generally be determined through history taking and detailed neurological examination, and can be confirmed by electrophysiological examination if necessary. Second, the type of peripheral nerve involvement is determined. Depending on the onset and progression of the disease, acute, subacute and chronic peripheral neuropathies are classified. According to the extent of nerve involvement, it is classified as mononeuropathy, polyneuropathy and polyneuropathy. Based on the type of pathology, they are classified as demyelinating and axonal neuropathies. The above classification is a guide for the etiological diagnosis of peripheral neuropathies and can narrow the differential diagnosis. Before the establishment of a wide variety of ancillary tests, the diagnosis of peripheral neuropathy often stopped there, and further etiologic diagnosis was very difficult. However, the rapid advances in ancillary testing have greatly improved the possibility of diagnosing the cause of peripheral neuropathy. Of course, the most direct and effective diagnostic tool is still the detailed medical history, both physical examination and later auxiliary examinations are based on the information provided by the medical history, the possible etiology, the possible differential diagnosis is cited, one by one, and finally the diagnosis is confirmed. Specifically, the diagnosis of peripheral neuropathy should pay attention to the following points: First, we must first determine whether the patient’s clinical symptoms and signs are consistent with the characteristics of peripheral nerve involvement or central nervous system involvement. Because certain central nervous system lesions such as spinal cord tumors, stroke, and multiple sclerosis can have clinical manifestations similar to peripheral neuropathy, especially when the patient complains of limb weakness. The following symptoms often suggest CNS involvement when present, such as diplopia, dysphagia, spasticity, epilepsy, and hemiparesis. If the patient’s sensory deficits are limited to the ipsilateral upper and lower extremities, the presence of a spinal cord or brain lesion should be considered. In general, peripheral neuropathy tends to have a more chronic progressive course than central neuropathy, and the common signs of peripheral neuropathy are decreased tendon reflexes, decreased muscle tone, and muscle atrophy. Second, clarifying the type of muscle weakness and sensory impairment of the patient, whether it is symmetrical or asymmetrical, whether it is predominantly distal or proximal, whether it is a peripheral neuropathy or a plexus or nerve root, is essential for the differential diagnosis of peripheral neuropathy. For example, if a patient presents with asymmetric acute or subacute sensorimotor impairment of a particular upper or lower extremity, cervical or lumbosacral radiculopathy, or vasculitis or plexus lesions or nerve entrapment or hereditary compression susceptibility neuropathy are often considered. Acquired demyelinating neuropathy is more likely to be considered if the patient presents with weakness and hyperalgesia with symmetrical proximal and distal involvement of all four extremities. If the patient presents with sensorimotor peripheral neuropathy with predominantly distal involvement of the extremities, axonal neuropathy is more likely to be considered. Third, distinguish peripheral neuropathy from neuromuscular junction lesions or myopathy. If the patient only shows symptoms of weakness without symptoms of sensory or autonomic nerve involvement, motor neuron disease, neuromuscular junction disease, or myopathy is mostly considered. Generally, elevated spasticity and tendon reflexes suggest upper motor neuron disease, while hypotonia, fasciculations and reduced tendon reflexes suggest lower motor neuron disease. Relatively preserved tendon reflexes, absence of sensory deficits, and elevated muscle enzyme profiles suggest myopathy. Neuromuscular junction lesions often involve the proximal limb muscles and the oculopharyngeal muscles, and patients often have easy fatigue. Fourth, if it is a single neuropathy then nerve entrapment syndrome should be considered. Local factors such as direct trauma, compression or impingement are often considered in the case of mononeural involvement, but systemic diseases such as hypothyroidism, diabetes mellitus, amyloidosis and rheumatoid arthritis must be excluded. Fifth, attention should be paid to the presence of other concomitant symptoms in addition to the manifestations of peripheral neuropathy, such as the presence of weight loss, the involvement of other organ systems, and the presence of skin pigmentation, with the aim of guiding further examination to find evidence of systemic diseases, toxic metabolic diseases, etc. If the patient has significant weight loss and peripheral neuropathy at the same time, nutritional deficiency neuropathy or paraneoplastic neuropathy should be considered. In addition, patients with certain psychiatric disorders such as depression, anxiety and sleep disorders may also present with limb weakness, which may be accompanied by sensory symptoms and need to be differentiated.