Wireless networking constitutes an important component of future information technology applications for both military and civilian purposes ranging from ad-hoc and sensor networks deployed in a battle-field to cellular networks with a very strong infrastructure. In order to design, implement and deploy highly reliable wireless networks, it is of utmost importance to address the presence of interference from other users in the system. In existing designs, interference is either avoided by a carefully chosen networking protocol (e.g. through time-division, space-division, frequency-division), or it is controlled to be near an acceptable level (e.g. through code-division). While simplifying the implementation, both of these commonly taken approaches are far from being optimal, and for reliable and efficient wireless networks of the future, a different look at the problem of handling the interference is needed. This research aims to develop explicit and practical coding/modulation solutions for multi-user communication channels, and to assess the possible gains with the enhanced physical-layer designs through end-to-end network simulation studies. In particular, a number of problems ranging from design of coding/modulation schemes for wireless interference channels, and two-way relay channels, to practical signaling for finite-input finite-output multi-user links are addressed. Both long block length coding/modulation solutions aiming at near capacity (or capacity bound) operation as well as short block length designs for delay sensitive applications are explored. Through these research activities, the project directly contributes to design and development of reliable wireless networks managing interference in an efficient manner, and to the field of general multi-user communications in a fundamental way. The project also integrates research and education generating many opportunities for undergraduate students to be involved in these activities.