Weakness is one of the most common complaints among the patients who were admitted to the emergency department. Sometimes the reason is identified but most of the time it remains unclear for clinicians. Weakness could be related to the nervous system (central and peripheral), metabolic disorders, electrolyte, endocrinopathy, cardiovascular disorders, paraneoplastic disease, vitamin deficiencies, toxins, infectious disease, and trauma. Due to various causes of weakness, it is helpful to limit the differential diagnosis thorough examination. There are different diagnoses for weakness. In patients with vague complaints such as weakness, their history should be taken carefully and perform clinical examinations to reach a definitive diagnosis.