The concept of Knowledge Management concerns the creation of structures that combine the most advanced elements of technological resources and the indispensable input of human response and decision making. This chapter addresses a very interesting topic—Knowledge Management (KM) and e-business initiatives within global organizations. It compares and contrasts the experiences of two global corporations as they have conceived and implemented KM initiatives. After in-depth secondary research on the subject, both companies developed their own KM in e-business strategy. The two case studies discussed in this chapter highlight Business-to-Business (B2B), Business-to-Consumer (B2C), and Business-to-Employee (B2E) initiatives at these two global organizations. This provides concepts and viewpoints related to the drivers of KM, the hurdles to KM in an organization, the elements of KM philosophy and process, how KM can come to be understood as a critical part of a company’s competitive strategy, and how to deploy a sustainable KM system that suits the business needs of an organization.