Research Summary: Entrepreneurial ecosystems command increasing attention from policy makers, academics, and practitioners, yet the phenomenon itself remains under‐theorized. Specifically, the conceptual similarities and differences of entrepreneurial ecosystems relative to, for instance, clusters, “knowledge clusters,” regional systems of innovation, and “innovative milieus” remain unclear. Drawing on research on industrial districts and agglomerations, clusters, and systems of innovation, we suggest that entrepreneurial ecosystems differ from traditional clusters by their emphasis on the exploitation of digital affordances; by their organization around entrepreneurial opportunity discovery and pursuit; by their emphasis on business model innovation; by voluntary horizontal knowledge spillovers; and by cluster‐external locus of entrepreneurial opportunities. We highlight how these distinctive characteristics set entrepreneurial ecosystems apart from other cluster types, propose a structural model of entrepreneurial ecosystems, summarize the articles in this special issue, and suggest promising avenues for future research. Managerial Summary: Entrepreneurial ecosystems command increasing attention from policy makers, academics, and practitioners. We suggest that entrepreneurial ecosystems differ from traditional clusters by their emphasis on the exploitation of digital affordances; by their organization around entrepreneurial opportunity discovery and pursuit; by their emphasis on business model innovation; by voluntary horizontal knowledge spillovers; and by cluster‐external locus of entrepreneurial opportunities. We highlight how these distinctive characteristics set entrepreneurial ecosystems apart from regional cluster phenomena discussed in received economic geography and innovation literatures. We suggest policy makers need to adopt novel approaches to stimulate entrepreneurial ecosystems that differ from those in place to develop industrial clusters or support already established small‐ and medium‐sized companies.