PURPOSE OF REVIEW: Heart failure (HF) is often accompanied by a constellation of comorbidities, leading to diverse patient presentations and clinical trajectories. While traditional methods have provided valuable insights into our understanding of HF, network medicine approaches seek to leverage these complex relationships by analyzing disease at a systems level. This review introduces the concepts of network medicine and explores the use of comorbidity networks to study HF and heart disease. RECENT FINDINGS: Comorbidity networks are used to understand disease trajectories, predict outcomes, and uncover potential molecular mechanisms through identification of genes and pathways relevant to comorbidity. These networks have shown the importance of non-cardiovascular comorbidities to the clinical journey of patients with HF. However, the community should be aware of important limitations in developing and implementing these methods. Network approaches hold promise for unraveling the impact of comorbidities in the complex presentation and genetics of HF. Methods that consider comorbidity presence and timing have the potential to help optimize management strategies and identify pathophysiological mechanisms.