In scientific efforts, we begin with hypotheses to be tested. A hypothesis is not a whimsical “what if”. A hypothesis, no matter how novel, must have a solid rationale and a clear experimental plan, but many times there are a number of plausible hypotheses, so often when hypotheses are tested, scientists disprove them. In fact, that is part of the joy of science. In drug discovery and development, failure is vastly more frequent than success and, in many cases, a decade or more of work by scores to hundreds of scientists and hundreds of millions of dollars may have been invested. Though such events are common, they are crushing to companies and the many people who worked so hard to get the answers that turn out to be negative. Many of these failures are of such a magnitude that they alter the future of the company and have very negative effects on careers. Whether the failure has a modest impact on a small group or a major impact on a company, they are devastating. Failures can happen despite the successful performance at every critical step by the team in charge of the effort. On the other hand, failures can be due to poor performance by the team, or the poor performance may be a factor in the failure. Therefore, it is vital to differentiate the two types of disappointments. In fact, it is always important to measure the team performance independently of the outcome. I made it a practice of congratulating the team if it earned congratulations, then saying that we were fortunate that the outcome was positive or vice versa.