This chapter argues that a combination of entrepreneurship and innovation is a crucial factor to the long-term sustainability of e-commerce and e-businesses. Entrepreneurship and innovation are positively related to each other and interact to help an organisation to flourish. The chapter takes an integrative approach to exploring the synergies between entrepreneurship and innovation and to analysing the factors that foster an interaction between the two. Case studies of entrepreneurial and innovative dot-com companies were conducted to complement a comprehensive literature review of entrepreneurship and innovation. This empirical study contributes to a better understanding of the existing theories and practices of entrepreneurship and innovation in organisations.