Botulinum toxin has long been known for its paralytic effects on the human voluntary musculature via inhibition of acetylcholine release at neuromuscular junctions. Its original clinical use for the treatment of strabismus has expanded significantly to include neurological conditions related to muscle hyperactivity and/or spasticity (e.g., dystonia, spasticity, tics, tremor, dysphonia). Recently, botulinum toxin has been shown to impact autonomic disorders by acting at acceptors on glands and smooth muscle, and consequently it has been used in the management of a number of other conditions including hypersecretory disorders, pain syndromes, detrusor sphinchter dyssenergia or overactivity and gastointestinal smooth muscle/sphincter spasm; it may also reduce pain in patients for whom it is used to treat these and other primary conditions. This article will review the pharmacology and formulations of botulinum toxins as well as data from clinical trials demonstrating their efficacy for numerous conditions based on their effects on cholinergic synapses outside the motor nervous system.