Muscarinic receptor antagonists form the mainstay of pharmacologic therapy for overactive bladder (OAB), a prevalent, debilitating, and costly condition. Antimuscarinics differ in their specificity for certain muscarinic receptors, their metabolism, and their ability to cross the blood-brain barrier. Trospium chloride is the only antimuscarinic that is a quarternary amine and its positive charge prevents the crossing of the blood-brain barrier, thus minimizing CNS side effects. Level I evidence supports the efficacy and tolerability of both the immediate-release and extended-release formulations of trospium. Furthermore, subanalyses of data pooled from large randomized, controlled trials support the efficacy is subpopulations such as men, the obese, and the elderly. The adverse event profile is favorable, with dry mouth and constipation presenting as the main adverse sequelae. As expected, CNS side effects have been rare and cognition does not appear to be impaired in those patients taking multiple medications.