Botulinum toxin is one of the most toxic natural substances; it acts by blocking the neuromuscular transmission by inhibiting Acetylcholine (Ach) releasing from the motor nerve into the neuromuscular junction. Although the toxin inhibits ACh release, other transmitters can also be inhibited. Botulinum toxin, specifically toxin type A (BONT-A) has been used since the 1970s to treat many different disorders, such as general spasticity resulting from stroke, multiple sclerosis or cerebral palsy, strabismus, hyperhidrosis or excessive sweating, pain, and it is effective in combating migraine and tension headaches. Since prostate gland is under the influence of autonomic innervation and associated neurotransmitters, the effects of BONT-A on the prostate have gained attention in the urological community and it has been studied in different species, including rats, dogs and humans. The aim of this paper is to review the mechanism of action of botulinum toxin and to discuss in particular the results of BONT-A treatment for benign prostatic hyperplasia (BPH), providing perspectives on potential therapy according to actual knowledge.