BACKGROUND Undergraduate students who are interested in biomedical research typically work on a faculty member's research project, conduct one distinct task (e.g., running gels), and, step by step, enhance their skills. This "apprenticeship" model has been helpful in training many distinguished scientists over the years, but it has several potential drawbacks. For example, the students have limited autonomy, and may not understand the big picture, which may result in students giving up on their goals for a research career. Also, the model is costly and may greatly depend on a single mentor. The NIH Building Infrastructure Leading to Diversity (BUILD) Initiative has been established to fund innovative undergraduate research training programs and support institutional and faculty development of the recipient university. The training model at Morgan State University (MSU), namely "A Student-Centered Entrepreneurship Development training model" (ASCEND), is one of the 10 NIH BUILD-funded programs, and offers a novel, experimental "entrepreneurial" training approach. In the ASCEND training model, the students take the lead. They own the research, understand the big picture, and experience the entire scope of the research process, which we hypothesize will lead to a greater sense of self-efficacy and research competency, as well as an enhanced sense of science identity. They are also immersed in environments with substantial peer support, where they can exchange research ideas and share experiences. This is important for underrepresented minority students who might have fewer role models and less peer support in conducting research. CONCLUSIONS In this article, we describe the MSU ASCEND entrepreneurial training model's components, rationale, and history, and how it may enhance undergraduate training in biomedical research that may be of benefit to other institutions. We also discuss evaluation methods, possible sustainability solutions, and programmatic challenges that can affect all types of science training interventions.