What makes entrepreneurship worth doing? While research on meaningful work has gained significant attention over the years, only recently has research begun to thoroughly examine this topic in the context of self-employment. Self-employment is a complex context for studying meaningful work, considering the positive and negative aspects of this type of work. On the positive side, the self-directed nature of self-employment, the primary focus of this chapter, offers autonomy and control over work that enables fulfilling aspirations, expressing one’s identity, and aligning personal values in work in ways that may be less feasible in employed work. On the other side, self-employment often entails long working hours, significant stress, and heightened responsibilities. This chapter provides a review of theoretical perspectives, methods, measurements, findings, and debates in the meaningful work literature to establish a theoretical foundation for research on meaningful work in the context of self-employment. We introduce the concept of entrepreneurial meaningfulness, which we define as the subjective global judgment that one’s work as an entrepreneur is personally significant and has positive valence. Entrepreneurial meaningfulness is shaped by work characteristics distinct to self-employment—ownership control, ownership responsibility, and ownership risk—as well as those found in traditional work contexts. We theorize that entrepreneurial meaningfulness will have a significant influence on important entrepreneurial outcomes, such as entrepreneurial persistence, well-being, and performance. We outline a research agenda to advance research on this important yet under-examined concept, which holds promise for broadening our understanding of what makes entrepreneurship worth doing.