Research conducted over the past 25 years has demonstrated that muscle activity, not neurotrophic substances, is the most important factor in the regulation of specific physiological and biochemical properties of muscle fibers. Application of this knowledge has led to considerable experimentation with chronic electrical stimulation as a possible clinical tool for the treatment of denervated muscles. Evidence accumulated from animal studies has indicated that direct electrical stimulation of denervated muscles can to a large extent substitute for innervation and preserve or restore the normal properties of the muscles. Appropriate stimulation parameters were critical for a successful intervention, and the best results were obtained when the stimulation pattern resembled the firing pattern of the normal motoneuron. Thus, fast muscles required intermittent, brief, high frequency stimulation and slow muscles needed continuous, low frequency stimulation. For human denervated muscles, critical questions still remain to be resolved before electrical stimulation will yield the optimum benefit. Research must be performed in human subjects to define the appropriate stimulation parameters, the stimulation current, and the type and placement of electrodes.