The medical field is one of the most exciting in America for entrepreneurs. Radiologists and other medical practitioners are in a unique position to take advantage of opportunities to invent and create innovative products and services. Physicians have led many of the most important revolutionary and evolutionary changes that have occurred in the field in the past 100 years. However, many radiologists find the process of entrepreneurship a daunting one and are often deterred from acting on their ideas. This article addresses the key issues and challenges that entrepreneurs face when embarking on new enterprises. Although most of these issues face all entrepreneurs at this stage, this article focuses on medical innovation and its particular challenges. This article concentrates on the kinds of questions that physician-entrepreneurs need to ask before jumping in, the types of common pitfalls that await those who don’t address these issues, and some answers to seek if you are to beat the odds and succeed.