What motivates patients to participate in clinical trials? Discussions most often revolve around potential study participants’ perception of therapeutic benefit. Misconceptions about therapeutic benefit can lead to an inappropriate motivation to participate in trials and incomplete understanding of the goals (and risks) of a clinical trial. This concept of “therapeutic misconception” is often the center of ethical discussions of clinical trials. Given clinical trials are designed to develop generalizable knowledge and are developed on the premise of clinical equipoise (in which there is no clear evidence of superiority of one treatment over another), investigators and society may suspect, and perhaps should expect, altruistic motives of study participants. In the case of clinical trials without the potential for therapeutic benefit (such as those projects participating in the BRAIN Research on Humans Consortium), the concept of altruism as a motivating factor becomes exponentially more important, as there is clearly no intended direct therapeutic benefit to the individual or society. Despite the key role of altruism in motivating participation in such studies, there are few systematic studies of altruistic motives or methods to assess and protect against altruistic vulnerabilities. Our overriding hypothesis is thataltruistic motives and intentions are complex and cannot necessarily be accepted at face value.