The recent devastating report from Lilly that the results from their Alzheimer clinical trial failed to demonstrate clinical effectiveness deals another hard blow to the patient and care giver community who participate in and support such trials. Unfortunately, the somewhat optimistic perspective I have heard expressed that the failure of yet another intervention aimed at decreasing the burden of beta-amyloid in the brains of persons suffering cognitive declines could “accelerate the pursuit of different research strategies” offers cold comfort. In reality, it is not that easy to change course in biomedical research. Once a dominant hypothesis becomes entrenched, the resources of the research enterprise are dedicated to investigations consistent with the orthodoxy. This can have a chilling effect on lines of research that question the status quo or pursue heterodox ideas. The reigning hypothesis determines the kind of training generations of scientists receive, the experimental and analytical models developed, and the tools and techniques invented. An important role for patient advocates and private funders is nurturing and sustaining alternative lines of research. Then, when failures accrue and new research strategies are called for, there will be a robust scientific community with different ideas to pursue. But first and foremost, well-grounded heterodox ideas have to be welcomed within the academy.