A clinical research team’s goal is to support the implementation, conduct, and monitoring of research studies and corresponding protocols. There is a need to ensure that study teams have adequate resources and regulatory support to successfully adhere to regulations and good clinical research practices. Our team, the UC Davis Division of Infectious Diseases Research Unit (IDRU), sought to establish a One Signature Initiative program for all studies and protocols supported by the IDRU. The One Signature Initiative designates one point of contact from each ancillary team or department to sign delegation and training logs, who in turn is delegated to train their team. The goals of the One Signature Initiative were, and are still, to reduce task redundancy, lessen regulatory burden on research teams, and minimize audit findings. Since the implementation of the One Signature Initiative in 2023, acceptance has been favorable, and we have expanded its footprint by incorporating it into our standard operating procedures. This article discusses our experiences, and ancillary departments’ experiences, with the One Signature Initiative. Our experience is an example of how a One Signature Initiative can be developed that is efficient, effective, and well-accepted by clinical research stakeholders.