For many years, physician-investigators have had a particularly difficult time with their academic careers, so that they have been labeled an endangered species. In this Invited Commentary, the author defines three career paths for physician-investigators-clinical researcher, clinician-scientist, and physician-scientist. Each of these pathways has common and distinct challenges that should be studied and potential improvements that should be evaluated through pilot research projects.The first challenge that all physician-investigators face is securing funding. Physicians are funded by their clinical activities, which often lures physician-investigators to increase their clinical work, particularly when research funding from the National Institutes of Health is difficult to secure and seemingly arbitrarily granted. The second challenge is an appointments, promotion, and tenure system that is not responsive to the needs of faculty working across clinical care and research, particularly when it comes to evaluating team science. Physician-investigators not working full-time in either discipline then may have trouble being promoted. The third challenge is the increasing burdens of clinical activities, particularly with the advent of electronic medical records.In this issue, two articles address overcoming the challenges faced by physician-investigators, one from the National Institutes of Health to grow the workforce and the other to offer organizational and individual solutions to support these investigators in faculty roles. These solutions are encouraging, but data about the extent of the challenges and the potential effects of the solutions are needed to make the physician-investigator career path less daunting.