Establishing an independent academic career is a lofty goal and junior physician-scientists have an especially complicated balancing act: caring for patients, conducting experiments and meeting regulatory requirements for human or animal subject research. This balancing act is often accompanied by teaching and administrative tasks, as well as the need to plan a coherent research program, obtain grant funding, and publish in scientific journals while, meanwhile, the clock is ticking. The effort requires a mix of scientific, technical, project management, and interpersonal skills. More intangibly, the path to independence requires flexibility, persistence, and self-confidence. Strong support from an academic institution, stronger support from a mentor and the ability to balance the many facets of both professional and personal responsibilities is essential. For those with such an inclination, successfully combining a clinical and research career can be quite rewarding but it is a career path that carries unique challenges and requires a specific skill set. This may explain why only 199 investigators have completed the clinical investigator programs designed to augment research training in medical residents in Canada since 1995. Establishing productive independence is an achievable goal and while there exists no “template for success,” our experiences of the transition to new investigator, many of which are echoed by colleagues, may identify some of the necessary skills and resources.