Patient centeredness is a concept that is increasingly being viewed as essential for clinical research. A core principle involves a comprehensive assessment and integration of patient and caregiver perspectives into trial design. Importantly, this involves more than just soliciting feedback. Patients and caregivers are now considered vital members of the study team, even serving as coinvestigators who may help to conceive, plan, and develop the study; continue to direct the day-to-day conduct of the study; and fully participate in the dissemination of the study results. The Patient-Centered Outcomes Research Institute offers substantial funding to support this approach, but getting started, particularly at institutions that lack a robust community engagement infrastructure, can be daunting. In this Special Communication, successful methods that have been used by researchers to engage patients, caregivers, and the broader health care community in the research process are outlined, and examples of currently funded studies that have fully engaged key stakeholders are described. Although trials are designed to assess efficacy and effectiveness and inform future implementation and dissemination, this Special Communication emphasizes methods to ensure trial results are relevant to and understood by the individuals and groups that they are intended to impact. Critical next steps in this new research approach are also discussed. In doing so, this will inspire future cardiovascular research that evaluates not only traditional end points, such as mortality and readmission, but also emphasizes true patient-centered outcomes, including quality of life, knowledge and satisfaction, caregiver burden, time tradeoffs, and out-of-pocket costs.