There has been a proliferation of patient-centric initiatives supporting drug development planning and execution during the past 24 to 36 months. Patient centricity seeks to engage patients and the health care community as drug development partners and represents a fundamental departure from a legacy product-centric research and development paradigm. As the clinical research enterprise gains experience, it is critical that it executes patient-centric initiatives well, provides sufficient support, sets realistic expectations and requires reasonable return on investment (ROI). This article offers insights and suggestions for organizations looking to establish ROI expectation and evaluation of their patient-centric initiatives. The article is based on ideas and concepts that have been shared and discussed among stakeholders throughout the clinical research enterprise.