Patients with heart failure (HF) have a significant morbidity and mortality that competes with those of many cancers. In HF patients with a severely depressed left ventricular function, and a wide QRS reflecting left ventricular dyssynchrony, cardiac resynchronization therapy (CRT) has been shown to improve functional capacity, HF symptoms, and quality of life. Since the first case reports were published in 1994, there have been a large number of randomized controlled clinical trials conducted that have proven the efficacy of CRT in diverse HF populations showing a significant reduction in HF hospitalization and improved survival. CRT has, over the past 25 years, become a guideline-indicated, evidence-based device therapy for mild and advanced HF patients with severely reduced left ventricular function, and a wide QRS. Nevertheless, there are a number of factors negating beneficial response to CRT, and multiple unresolved questions to this day. This review article summarizes current available knowledge on CRT in HF patients from randomized clinical trials and other relevant studies, discusses important determinants of CRT response, and provides a selected overview of unresolved questions with future directions for research.  Kulcsszavak: Cardiac Resynchronization Therapy, Left Ventricular Dyssycnhrony, Clinical Outcomes, Clinical Trials, Future Directions