Randomized controlled trials are the most unbiased way to evaluate many types of healthcare interventions. Pharmaceutical and medical technology industries play an important role in developing and testing new interventions that have commercial potential. However, many interventions for the prevention, treatment and rehabilitation of stroke are either not drugs or devices or have no commercial potential. Like many other clinicians who are uncertain about the value of existing or new treatments, we are involved in investigator-led clinical trials to resolve treatment uncertainties. There is common agreement that investigator-led clinical trials are facing increasing difficulties and that as a result clinicians may be deterred from pursuing clinical trials as a research career. In this article, we express our concerns for the future of such trials, balanced with the hope that systems to foster and sustain this important type of research in the future can be developed.