This paper provides a systematic review of the literature on how small and medium-sized enterprises (SMEs) use and acquire knowledge. The review was undertaken as part of the Economic and Social Research Council's Evolution of Business Knowledge Programme. The paper describes the systematic review protocol and provides a detailed explanation of the methods used. From the review, it is evident that SME knowledge research concentrates primarily on the acquisition and use of knowledge, treating it as an asset that is transferred by routines. The findings suggest that research is focused in three main areas. First, on the influence and abilities of the entrepreneur to extract, use and develop knowledge resources. Secondly, on firm-wide systems and the social capital that facilitates knowledge exploration and exploitation. Thirdly, on the provision of knowledge and learning experiences through government policy. From a practical perspective, the review concludes that policies encouraging entrepreneurship and economic regeneration need to be more flexible and sensitive to the often complex contexts within which knowledge is used by SMEs. From a research perspective, and given the flexible, opportunity-oriented and often novel nature of SMEs identified in these studies, there is a need to consider the relational and embedded qualities of knowledge by which these characteristics are framed; qualities that resist conceptualization as some form of separable, material asset.