Suboptimal adherence and persistence to therapy are major challenges for patients treated with ocular hypotensive medications. The problem affects 5% to 80% of glaucoma patients from all nations, ethnicities, socioeconomic backgrounds, and education levels. Although health care providers are generally poor at detecting suboptimal or poor adherence in the clinical setting, several strategies to systematically assess adherence and persistence rates are available. One strategy involves electronic monitoring of patient dosing, which provides useful insights into specific patterns of adherence behavior among glaucoma patients. Adherence behavior is complex with multiple interrelated determinants; these can be broadly grouped into provider factors, environmental factors, medication factors, and patient factors. Targeted patient education strategies, counseling, electronic monitors, alarms, and reminders have all been used in efforts to improve adherence. These interventions probably work best in combination. Identifying tangible barriers to adherence and simple strategies to overcome these through an open, discursive relationship between clinician and patient is key to optimizing adherence.