The neurophysiology of amyotrophic lateral sclerosis is important not only in relation to diagnosis, but also in the development of methods to follow progress, and the effects of putative therapies, in the disease. Quantitative techniques can be applied to the measurement of reinnervation using needle electromyogram. The methodology of motor unit number estimation may be useful in measuring loss of functioning motor units in groups of patients but variability in the measurement using current methods limits its sensitivity in the evaluation of individual patients. Conventional neurophysiological measurements, expressed as a multimetric index, may be useful in assessing progress. The cortical and upper motor neuron system can be assessed using transcortical magnetic stimulation protocols, and cortical excitability may be measured by the peristimulus histogram method. In this review the advantages, limitations and promise of these various methods is discussed, in order to indicate the direction for further neurophysiological studies in this disorder.