Advances in the care of critically ill patients are dependent upon rigorous clinical research undertaken to characterize natural history and risk factors, and determine optimal approaches to the management of the diseases of the critically ill patient. The Canadian Critical Care Trials Group (CCCTG) was formed in 1989 to foster such research. It has grown to become a national, multidisciplinary organization with more than 100 members, and more than 3 dozen active research programs. Its members have been highly successful in obtaining funding for, completing, and publishing well-designed studies that have informed international practice in areas such as transfusion, stress ulcer prophylaxis, long term outcomes from acute respiratory distress syndrome, diagnosis and management of infection in the intensive care unit, and end-of-life care. In the process, the CCCTG has developed a highly effective culture of scientific mentoring, and has served as a model for investigator-led critical care research groups around the world. This review summarizes the history, activities, approaches, and challenges of the CCCTG, in the conviction that investigator-led groups such as ours represent the future of intensive care unit-based research.