PURPOSE OF REVIEW: Muscle weakness is a common feature of many neuromuscular disorders. This article outlines a symptoms and signs approach to the patient presenting with neuromuscular weakness, highlighting key aspects of the clinical history and examination.RECENT FINDINGS: The past several years have seen a dramatic increase in the ability to test for many inherited and autoimmune neuromuscular disorders more reliably and accurately. Similarly, numerous targeted therapies have been recently approved to treat previously untreatable disorders. Therefore, timely and accurate diagnosis is essential so that patients can receive appropriate therapy, ultimately leading to better clinical outcomes.SUMMARY: Muscle weakness is a common symptom resulting from dysfunction that can occur at any level of the neuraxis and is a cardinal feature of many neuromuscular disorders. An accurate and meticulous history and a thorough neurologic examination are paramount in localizing the lesion in order to generate a differential diagnosis and guide appropriate ancillary testing. The patient's age at symptom onset, any identified inciting factors, tempo of symptom progression, pattern of weakness, and associated symptoms and signs are all important diagnostic clues in the evaluation of a patient presenting with muscle weakness.