With the increasing availability of therapeutic strategies and the growing complexity of health care delivery for patients with heart failure, objective evidence of the tangible benefits of different approaches to care is needed. Comparative effectiveness research (CER) offers an important avenue for making progress in the field. CER, like any well-designed research program, requires articulation of clinically important outcomes to be compared. In this review, available CER end-point domains are discussed, the wide variety of end points used in CER are summarized, and future steps for greater standardization of end points across heart failure CER are suggested.