The clinical hallmark of myasthenia gravis (MG) is fluctuating, painless weakness of muscles that most often affect extraocular, lower bulbar, or limb musculature. Predicting the probability of successful treatment for the patient assumes that the physician has made an accurate diagnosis. In this review, the practical differential diagnosis of MG is reviewed from the perspective of conditions (at presentation of symptoms and signs) that may mimic the disorder. The differential diagnosis includes disorders that limit eye movements (with or without associated diplopia), cause false-positive laboratory studies, and mimic MG but have normal eye movements. The differential diagnosis includes disorders that affect the upper brainstem, cranial nerves, neuromuscular junction, muscles, or local orbit anatomy. Nonneurological systemic diseases (i.e., encephalopathy, sepsis) can produce fluctuating ptosis or eye movements that can occasionally be confused with MG. Although MG is considered often in the differential diagnosis of weakness or fatigue symptoms that lack a correlate on neurological examination (subjective fatigue, breakaway weakness, chronic fatigue syndrome), MG is almost never found.