OBJECTIVE: To review the evidence on adherence with bisphosphonates and evolving dosing strategies for osteoporosis treatment. DATA SOURCES: Articles were identified by searching MEDLINE (1975-December 2005) using the following terms: osteoporosis, postmenopausal, fracture, adherence, compliance, persistence, drug therapy, bisphosphonates, alendronate, risedronate, ibandronate, and zoledronate. Additional data included bibliographies from identified articles. STUDY SELECTION AND DATA EXTRACTION: All pertinent English-language articles that discussed adherence issues in patients with osteoporosis were included. Both those that reviewed overall issues of medication adherence in osteoporosis and those that focused specifically on adherence to bisphosphonates were included, as were articles that addressed strategies for overcoming nonadherence. DATA SYNTHESIS: Inadequate diagnosis and treatment of osteoporosis result in a higher risk of fractures than is necessary. Even patients who are diagnosed and beginning treatment often do not persist with their osteoporosis medication because they perceive their fracture risk to be low and, given the asymptomatic nature of osteoporosis, do not experience the benefit of symptom reduction after taking the drugs. Factors that affect adherence to osteoporosis therapy include drug costs, adverse effects, dosing frequency, disease education, patient follow-up, and patient involvement in treatment decisions. CONCLUSIONS: By considering and implementing strategies that can improve adherence and persistence, primary care providers and pharmacists (via counseling) may enhance long-term outcomes for patients with osteoporosis.