Depression is common among patients with heart disease. It is an important comorbidity, both because of its well-known effect on the quality of life and also because it has a significant impact on the ability of patients with heart disease to engage in healthy behaviors and to avoid unhealthy ones. In addition, depression is associated with increased morbidity and mortality in those with established cardiovascular disease. However, no study has demonstrated that treatment of depression improves cardiac outcomes in patients with heart disease. Some have argued that additional trials are not necessary, and that the importance of depression argues for increased recognition and treatment even if it cannot be demonstrated that this improves morbidity and mortality. This article makes the case for more trials in this area, highlighting the importance of using the results of prior trials to generate hypotheses and provide directions for future studies in this area and noting the effect that demonstrating improved survival might have on clinical practice.