E-collaboration takes advantage of the current Internet-driven business environment, which integrates the most advanced electronic technologies and the knowledge-based economy. Companies engaging in e-collaboration must participate in external business relationships by using computer interactions (Damanpour, 2001). Implementing e-collaboration strategy can require many sophisticated technologies and systems such as EDI, XML, eCRM. E-collaboration is thus confronted with the great challenge of reengineering IT strategies and resources. “Nearly 80% of organizations that have rushed to establish Web sites for online retailing have failed to invest in the purchasing and distribution systems that make delivery of their products possible” (Neef, 2001, p.3). System failure has a profound effect on e-collaboration and e-business, both in the short and long-term. The tremendous complexity of information technologies has become a huge hurdle to companies embracing them, affecting their entire management strategy, process, structure, and most importantly, business bottom line results. The main technological issues to be considered are associated with IT infrastructure, and managers’ and operatives’ knowledge and skills in e-collaboration and e-partnership. The following constitutes some of the key technological issues facing e-collaboration. • Process and system alignment and integration • Interoperability of systems • Accessibility, security and compatibility of interorganizational information systems • Traffic in collaborative e-commerce activities • Sustained IT support and resources • Transferring and sharing information and data • Building and sustaining an effective virtual network structure amongst e-partners • Quality and effectiveness of networking and communications (Zhao, 2004) This article focuses on the most important technological challenges and issues facing e-collaboration and e-business in the areas of information flow, procurement, logistics, engineering and manufacturing, marketing, customer services, and human resources. It deals specifically with the process and system alignment and integration as well as the issues of interoperability which have become of primary concerns in the practices of e-collaboration.