The effects of regulations on small and medium-sized enterprises (SMEs) have garnered significant political attention internationally, yet, in the academic literature, these effects remain contested. This article presents findings from a systematic literature review of qualitative evidence on the effects of regulation on SMEs. It sets out the strengths of qualitative approaches in relation to more prominent and influential quantitative approaches. It conducts a thematic synthesis of the qualitative research to develop a conceptual framework that provides a processual, embedded understanding of the effects of regulations on SMEs. The conceptual framework highlights four key, interconnected processes: identification-interpretation; strategization; negotiation; and adaptation. This conceptual framework generates insights into dynamic and potentially indirect effects of regulations in relation to a complex array of influences external to and within the business. On the basis of these insights a new research agenda is proposed.