Lower urinary tract symptoms (LUTS), overactive bladder syndrome (OAB) and detrusor overactivity (DO) are all conditions that can have major effects on quality of life and social functioning. Antimuscarinic drugs are first-line treatment-they often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, and alternatives are needed. The recognition of the functional contribution of the urothelium, the spontaneous myocyte activity during bladder filling, and the diversity of nerve transmitters has sparked interest in both peripheral and central modulation of LUTS/OAB/DO pathophysiology. There may be several new possibilities to treat LUTS/OAB/DO. β(3)-AR agonists (YM178), PDE 5 inhibitors (sildenafil, tadalafil, vardenafil), vitamin D analogs (elocalcitol), combinations (α(1)-AR antagonist + antimuscarinic), and drugs with a central mode of action (tramadol, aprepitant) all have Randomized controlled trial (RCT) documented efficacy. Which of these therapeutic principles will be developed to clinically useful treatments remains to be established.