Personalized medicine is a form of medicine that uses the patient's genomic information to improve diagnosis, prevention and therapy. In this review we discuss the personalized management of heart failure, from monogenic disorders, to modifier genes and pharmacogenomics. Monogenic disorders causing heart failure are cardiomyopathies. In this disease, recent guidelines assist the clinician in molecular diagnostics, genetic counseling and therapeutic choices. Several lines of evidence suggest the existence of common polymorphic variants of genes that modify the susceptibility to heart failure (modifier genes). A candidate gene approach has shown that common genetic variants of the renin-angiotensin-adrenergic pathway can also influence heart failure and may be associated with different outcomes. However, still little is known regarding this and it is expected that more advanced high throughput technologies will allow the discovery of a number of novel modifier genes that could be used for prognostic profiling and development of novel therapeutics. Finally, pharmacogenomics of heart failure appears very promising. Common genetic variants of beta-adrenergic receptors, alpha-adrenergic receptors and endothelin receptors, among others, significantly alter the response to heart failure therapy. This knowledge could be used to personalize and optimize heart failure therapy based on the patient's genetic profile. Whereas the advances in technologies will continue to transition personalized medicine from research to the clinical setting, physicians, and in particular cardiologists, need to reshape clinical diagnostics paradigms, learn how to use new genomic information to change management decisions, and provide the patients with appropriate education and management recommendations.