The neuromuscular junction is a specialized myoneural synapse that is a target for a variety of disorders including autoimmune origin. Although myasthenia gravis, the most common autoimmune neuromuscular junction disorder, is characterized by weakness of muscles that increases with repetitive use and improves with rest, disorders of the neuromuscular junction have a wide range of clinical presentations. This frequently poses a diagnostic challenge to clinicians. The exact diagnosis of neuromuscular junction disorders requires detailed history and physical examination, several pharmacological methods, neurophysiologic testing, and serologic or immunologic tests. The clinical presentation determines which diagnostic tests should be used in patients with these disorders.