The increasing longevity of patients with heart failure (HF) and the rise in the incidence of HF has created an urgent need to effectively treat and prevent left ventricular remodeling. Within the past 6 years, skeletal myoblast and bone marrow mononuclear cell transplantation have been undertaken in over 200 patients with HF, geared to the underlying injury, not just its mechanisms. Early safety/feasibility studies showed promising but somewhat conflicting secondary symptomatic and functional improvements, and safety concerns have arisen. However, the patient population, cell type, dose, time, mode of delivery, and outcome measures differed—making comparisons problematic. It is now time to: 1) create a central registry of all patients treated with cells; 2) perform side-by-side comparisons of different types of cells in patients with similar HF states; 3) agree on standardized trial designs; and 4) define acceptable and unacceptable outcomes (and measures) compared with both standard of care and to other emerging therapies. By doing so, we can avoid the pitfalls that previous biologics (eg, angiogenic gene therapy) have suffered, increase the likelihood of success, shorten the time-to-presentation of cell-based algorithms to clinicians, and deliver these therapies to patients who await new ways of reduction of symptoms and improvement of quality of life.