In this review we evaluate clinical neurophysiological methods, originally described for use in diagnosis that can be applied to measurement of change during the progress of amyotrophic lateral sclerosis (ALS). Such measurements are potentially important in clinical trials, and also in clinical practice. We have assessed methods for lower and upper motor neuron function, including conventional EMG, nerve conduction and F-wave studies, the derived Neurophysiological Index, motor unit counting methods (MUNE), and transcranial magnetic motor cortex stimulation. We have also addressed the validity of measurements of electromechanical coupling. Methods for measuring muscle strength are beyond the scope of this review. We conclude that MUNE, M-wave amplitude and the Neurophysiological Index are sufficiently reliable, sensitive, and relevant to the clinical problem of ALS, to be used in clinical trials in the disease. Transcranial magnetic stimulation is of limited value, but a combination of the measurements made as part of this technique may also be useful. We conclude that clinical neurophysiological techniques should now be used in measuring change in clinical trials in ALS.