Heart failure is a complex clinical syndrome affecting around 70 million individuals globally. It has a prevalence of 2% in Europe and North America and approximately 1% in Asia and South America. Accurate diagnosis relies on the presence of typical signs and symptoms, elevated natriuretic peptide concentrations, and evidence of cardiac structural or functional abnormalities using cardiac imaging techniques. Approximately half of all heart failure cases are attributed to reduced left ventricular systolic function-classified as heart failure with reduced ejection fraction (HFrEF). Current guideline-directed medical therapy has markedly improved survival and quality of life for patients with HFrEF. Contemporary management emphasises early initiation and rapid uptitration of four foundational drug classes-renin-angiotensin system inhibitors or angiotensin receptor-neprilysin inhibitors, β blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors-alongside diuretics for the symptom relief of volume overload. Despite advances in management, heart failure remains a leading cause of cardiovascular morbidity and mortality, partly due to absence of implementation of, and poor adherence to, medications. Future directions to improve outcomes include the integration of personalised medicine approaches, multiomic profiling, and innovative clinical trial designs to address residual risk and identify novel therapeutic targets. This Seminar provides an overview of the current diagnostic and pharmacological management of patients with HFrEF, highlighting the progress and outlining the challenges that remain.