This article will discuss many of the key concepts regarding chemodenervation and neurolysis in the management of spasticity. Topics that will be discussed include techniques for localization, strengths and limitations of various agents (botulinum toxin, phenol, and alcohol), the value of combination therapies, and the role of nerve blocks (diagnostic and therapeutic). With advancing technology have come newer methods to improve accuracy of localization for the performance of chemodenervation and neurolysis such as electromyographic guidance, electrical stimulation, and ultrasound guidance. During the last 2 decades, the addition of botulinum toxin chemodenervation as an adjunct to traditional neurolysis, medication, and therapy modalities has expanded the field of treatment of intramuscular hyperactivity in upper motor neuron syndrome. The technique of diagnostic blocks as predictors of response and the therapeutic value of nerve blocks will be discussed.