In reflecting on the differences between successful and unsuccessful clinical trials or programs, several factors consistently emerge as essential components of success and failure. Although all are largely within control of developers, many are often inadequately considered or overlooked. There is no doubt that many companies work diligently to design and conduct only the most scientifically sound clinical studies. The goal of this paper is to remind us of the importance of these essentials so that effective therapies have a greater likelihood of reaching patients.