This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the American Heart Association held in Chicago in 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. In patients with mild heart failure (HF), EMPHASIS-HF showed that the addition of eplerenone to standard therapy was well tolerated and reduced both the risk of death and hospitalization. The addition of cardiac resynchronization therapy to implantable cardioverter defibrillator (ICD) therapy reduced the incidence of all-cause mortality and HF hospitalizations in patients with NYHA class II-III HF compared with ICD alone in RAFT. Telemonitoring failed to improve outcome compared with a high standard of conventional care in patients with chronic HF (TIM-HF study) and a telephone-based interactive voice response system failed to improve outcome in patients recently hospitalized for HF (Tele-HF study). ASCEND-HF suggested that nesiritide was ineffective but safe in patients with acute decompensated HF. ROCKET-AF suggests that the factor-Xa inhibitor rivaroxaban may be as effective as warfarin in patients with atrial fibrillation. The PROTECT study provided more data to suggest that amino-terminal B-type natriuretic peptide guided therapy may be beneficial in patients with left ventricular systolic dysfunction.