A limitation of recent work in the analysis of information systems strategies (ISS) for small-to-medium enterprises (SMEs) is the tendency to focus exclusively on organisational resources as being the only source of competitive advantage. In some knowledge-based SMEs, ISS involves competitive advantage being obtained through a variety of mechanisms. These mechanisms include interfirm relationships and industry-structure as well as resources. This paper develops a framework for analysing ISS deployed by Australian biotechnology SMEs in one of the most knowledge-intensive industries. By making IS research conscious of the variety of ways SMEs source competitive advantage, at organisational, relational-based and industry structural levels, it is anticipated that the paper will contribute to the on-going debate on ISS and SMEs in the evolving knowledge economy.