Assessment of the risks versus the benefits of hormone replacement therapy has become a challenging task for the physicians. Controversial issues have surrounded the status of hormone replacement therapy for postmenopausal women lately. Several randomized controlled trials present contradicting evidences and have raised questions about the short-term risks of long-term benefits of HRT. Evidence from clinical trials like the WHI and HERS trial does not support HRT use for prevention of cardiovascular disease. The review also discusses the association of hormone replacement therapy and cancer, stroke, cognition, cardiovascular disease, venous thromboembolism, osteoprosis, gall bladdaer disease, and quality of life. The latest controversial results of randomized controlled trials in recent years have posed newer challenges for the physicians in prescribing HRT for postmenopausal women.