Although scientists are continually refining existing knowledge and producing new evidence to improve health care and health care delivery, far too little scientific output finds its way into the tool kits of practitioners. Likewise, the questions that clinicians would like to be answered all too rarely get taken up by researchers. In this article we focus on knowledge translation challenges accompanying a longitudinal research program with nonprofit organizations providing direct and indirect health and social services to disadvantaged groups in one region of Canada. Three essential factors influencing authentic and reciprocal knowledge transfer and utilization between nonprofit service providers and researchers are discussed: strong institutional partnerships, the use of skilled knowledge brokers, and the meaningful involvement of frontline personnel.