Lower urinary tract symptoms (LUTS) can be categorized as storage, voiding, and postmicturition symptoms. Although often associated with benign prostatic hyperplasia (BPH), they may also occur in women. This observation, the beneficial effects of ⍺-adrenoceptor (AR) antagonists in men with BPH and LUTS, and the frail correlation between LUTS, and prostatic enlargement and/or outflow obstruction have focused interest on the role of extraprostatic ⍺-ARs in the pathogenesis of LUTS. It has been suggested that an upregulation of contraction-mediating ⍺-ARs and a downregulation of relaxation-mediating β-ARs can contribute to LUTS generation. However, recent investigations on human bladder tissue could not confirm such a change. Antimuscarinic agents are effective for treatment of the overactive bladder, which is characterized by urge, frequency, urge incontinence, and nocturia (ie, LUTS). This suggests that muscarinic receptors are involved in the pathogenesis of LUTS, and there is recent evidence implicating purinergic receptors. Structural changes in the bladder, such as smooth muscle hypertrophy and connective tissue infiltration, are associated with detrusor overactivity in about 50% to 66% of patients with BPH. However, it is unclear whether this is caused by bladder outlet obstruction because the symptoms may remain in up to 33% of the patients after surgical removal of the obstruction. When outflow obstruction is reversed in rats, there is a subset (20%) that continues to have overactive voiding, despite a reversal of the bladder hypertrophy, suggesting that changes within the central nervous system may be a contributing factor. LUTS can be caused by many, often overlapping, pathophysiologic mechanisms, which may contribute to individual variation in response to treatment.