Pharmacologic treatment of heart failure has progressed over the last two decades, but regimens have become more complex. With pharmacogenetics, the time is rapidly approaching when information on genetic variability will be used to predict therapeutic response and select the right drug for the right patient. In this issue of Heart Failure Clinics, several leading pioneers of this next revolution in heart failure treatment present the current state-of-the-art on the use of genomic information to target therapeutics. The issue begins with two articles on the basics of what every clinician needs to understand to apply genomic information to patient care and a historical overview of the move toward genetically targeted therapies. The articles that follow address specific therapeutic interventions such as neurohormonal inhibitors and beta blockers. The next series of articles address the genomics of hypertension, left ventricular hypertrophy, and how genomic differences may underlie the apparent racial differences in heart failure and therapeutics. The final third of the issue turns to how genomics will assist treatment of specific clinical scenarios, including myocarditis, transplant rejection, device therapy and pulmonary arterial hypertension. The issue concludes with a discussion of genome-wide association studies.