In the midst of all the buzz about Risk-Based Monitoring (RBM), focus has largely been on defining a Sponsor/CRO’s methodologies for risk-assessment and adjusting monitoring activities to most effectively address those risks. It seems less attention has been paid to the impact these new strategies have had on the clinical sites that play the role of first line of defense for quality data and patient safety. The purpose of this white paper is to bring the clinical site’s experience of RBM to light through a review of recent developments and resources focused primarily on clinical research site viewpoints. Drawing from the expertise of industry authorities, including the collective experience of NAMSA’s own clinical personnel, this document provides recommended methods for Sponsor/CROs to address concerns in an effort to strengthen the partnership with clinical sites, thereby enhancing the quality and functionality of the RBM approach. The three biggest areas of concerns were found to be a lack of consensus and understanding between site and Sponsor/CRO in regards to the nature and implications of a risk-based approach, concerns regarding fair compensation for the change in services the site provides and the tasks which they are asked to perform, and a challenge to relationships and communication between site and Sponsor/CRO. By utilizing strategies such as early education on RBM, transparent and creative budgeting, and a deliberate approach to maintaining partnerships, the Risk-Based monitoring trial has the potential to strengthen relationships and quality of clinical trials.