Entrepreneurs frequently work in highly unpredictable environments and are involved in a wide variety of tasks for which they are often ill prepared. Good mental health is of utmost importance to adequately manage the challenges, adversity, and stressors that come with running a business. However, little is known about how mental health affects entrepreneurs and the performance of their businesses. Drawing on the literature of personality and entrepreneurial exit as well as on evidence from large-scale survey data on the relation between depression and entrepreneurial exit, we show that there is ample opportunity for research investigating the relation between mental health and entrepreneurship. Five directions for future research on this topic are highlighted.