For decades, diuretic therapy has been a cornerstone in treating hypertension, an approach supported by multiple randomized controlled trials demonstrating reduced morbidity and mortality from cardiovascular events. Yet controversy persists regarding the potential detrimental metabolic effects and side effects of diuretic agents. Within the risk-benefit debates about diuretic therapy is a second dialogue regarding the best thiazide or thiazidelike agent to prescribe. Proponents of chlorthalidone emphasize the demonstrated reductions in cardiovascular events reported from multiple classic trials and its longer half-life, whereas opponents point to its limited availability in low-dose forms and comparable favorable results from hydrochlorothiazide-based therapy to discredit claims of superiority. This review presents the data available on both sides of this issue to help the reader decide which claims are most valid, and offers recommendations for treatment.