E-commerce is often associated with the buying and selling of consumer products over the Internet. While this narrow definition of e-commerce is correct, many other commerce and business activities also fall under the term “e-commerce”. The stakeholders who create commerce, either actively or passively construct and determine the nature of the commercial relationship. The aim of this chapter is to suggest the e-commerce Differentiation Framework, which uses the nature and activities of stakeholders to distinguish between the two major types of e-commerce, namely Business-to-Business (B2B) e-commerce and Business-to-Consumer (B2C) e-commerce. This framework will use examples of e-commerce in Small and Medium Enterprises (SMEs) in Singapore and Australia. The study was carried out in these two countries over a period of four months in 1999.