The interplay between health, entrepreneurship and small and emerging businesses is a research field receiving growing interest. Studies point to both health-related risks and opportunities, which have implications for the social and economic lives of entrepreneurs and employees in small and new firms. Research has been carried out in different disciplines, which have contributed in different ways to the understanding of this inquiry. As the field is still premature and interdisciplinary in nature, there is a need to establish boundarycrossing avenues for developing new knowledge on the topic. This ambition has led to the development of this special issue. The issue includes results from original research on working life challenges encountered by small and new businesses, approached from a variety of disciplines. In this introduction, we begin by tracing an overarching framework, to which we add brief descriptions of the contributing papers. To conclude, we outline future research goals and discuss how issues around mental health, regulation and work environment inspections, race, disability and gender issues and the growing gig economy will affect the conditions for healthy entrepreneurial work.