Overactive bladder syndrome (OAB) is a chronic condition that has an impact on patients’ daily activities and health-related quality of life (HRQL). Anticholinergic therapy is often prescribed following insufficient results with behaviour modification alone; however, rates of treatment discontinuation are consistently high. This study systematically reviewed persistence and adherence data in patients with OAB treated with anticholinergic therapy. A search focused on the intersection of OAB, persistence/adherence, and anticholinergic therapy was conducted in MEDLINE and EMBASE. Articles published after 1998 were reviewed and selected for inclusion based on prespecified criteria. A total of 147 articles and two abstracts were included in the review. Results from 12-week clinical trials showed high rates of discontinuation, ranging from 4% to 31% and 5% to 20% in treatment and placebo groups, respectively. Unsurprisingly, rates of discontinuation found in medical claims studies were substantially higher, with 43% to 83% of patients discontinuing medication within the first 30 days and rates continuing to rise over time. Findings from medical claims studies also suggest that over half of patients never refill their initial prescription and that adherence levels tend to be low, with mean/median medication possession ratio (MPR) values ranging from 0.30 to 0.83. The low levels of persistence and adherence documented in this review reveal cause for concern about the balance between the efficacy and tolerability of anticholinergic agents. Strategies should be identified to increase persistence and adherence. New agents and non-pharmacologic alternatives with good efficacy and minimal side effects should be explored.