Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of unclear etiology. Diagnostic challenges often appear already at the early stage of the disease. Detecting developed neuropathies on time, including multifocal motor neuropathy with a conduction block, allows administering a treatment, which can prove to be successful quickly. Electrophysiological studies assess the lesion of the peripheral and central motor neuron and serve as markers supporting the diagnosis of ALS. Electromyographic and neurographic studies make it possible to take an objective look at the involvement of the peripheral nervous system and constitute, apart form the clinical assessment, an important element of the ALS diagnosis. Transcranial magnetic stimulation, augmented with a new method of triple stimulation technique (TST) helps in the diagnosis of lesions in the cortico-bulbar and cortico-spinal tract in patients with no clinical symptoms of the upper motor neuron involvement. Additionally, this technique allows making the diagnosis of the conduction block localized in the proximal nerve segments, especially when the results of neurographic studies are not unequivocal. In experimental studies assessing responses to treatment attempts and monitoring the development of the disease there has been used the MUNE method (motor unit number estimation), which informs of the number of active motor neurons. In this review there have been described the up-to-date electrophysiological methods, facilitating the diagnosis and monitoring of the progressive lesion of the lower and upper motor neuron in patients with amyotrophic lateral sclerosis. Besides, there have been presented other clinical syndromes, which must be distinguished from amyotrophic lateral sclerosis.