There are multiple evidence-based drug treatments for chronic heart failure (HF), both disease-modifying agents and those for symptom control. The majority of the evidence base supports drugs used in HF with reduced left ventricular ejection fraction. The mainstay of disease modification involves manipulation of neurohormonal activation that occurs in HF. In addition to established angiotensin-converting enzyme inhibitors, beta blockers and mineralocorticoid receptor antagonists (MRAs), newer agents are now available such as the angiotensin receptor neprilysin inhibitors. Achieving the optimal drug regimen is complex and best performed by a specialist heart failure team. We aim to provide a comprehensive overview of contemporary drug therapies in chronic heart failure, as well as practical guidance for their use. There is a focus on treating patients with challenging comorbidities such as hypotension and chronic kidney disease (CKD), where a thorough understanding of drug therapy is essential. Multiple trials assessing the benefits of new therapies in HF, such as intravenous iron, are also ongoing.