The author analyses problems and challenges faced by state of the art wireless multiple access technologies and presents series of new approaches and methodologies to address some of the most critical problems limiting the capacity and reliability of multi-user CDMA wireless communication. The introductory chapter is dedicated specifically to provide a thorough review of key concepts of multi-user wireless communications and motivations that fuelled the research work in subsequent chapters. The work cover important research areas such as multi-user detection, adaptive interference estimation and cancellation and how the new techniques presented here can substantially increase the capacity of CDMA. Review of Cooperative Communication, how it enhances the link performance by providing diversity without use of antenna arrays, its limitations and ways to achieve maximum performance in multi-user settings are presented. Finally a novel approach of collaborative spreading that is designed to substantially increase the capacity of CDMA without compromising the detection performance and complexity even under very high user overloading conditions is investigated.