This dissertation addresses some of the most important issues in delay-sensitive communication over wireless systems and networks. Traditionally, the design of communication networks adopts a layered framework where each layer serves as a "black box" abstraction for higher layers. However, in the context of wireless networks with delay-sensitive applications such as Voice over Internet Protocol (VoIP), on-line gaming, and video conferencing, this layered architecture does not offer a complete picture. For example, an information theoretic perspective on the physical layer typically ignores the bursty nature of practical sources and often overlooks the role of delay in service quality. The purpose of this dissertation is to take on a cross-disciplinary approach to derive new fundamental limits on the performance, in terms of capacity and delay, of wireless systems and to apply these limits to the design of practical wireless systems that support delay-sensitive applications. To realize this goal, we consider a number of objectives. 1. Develop an integrated methodology for the analysis of wireless systems that support delay-sensitive applications based, in part, on large deviation theory. 2. Use this methodology to identify fundamental performance limits and to design systems which allocate resources efficiently under stringent service requirements. 3. Analyze the performance of wireless communication networks that takes advantage of novel paradigms such as user cooperation, and multi-antenna systems. Based on the proposed framework, we find that delay constraints significantly influence how system resources should be allocated. Channel correlation has a major impact on the performance of wireless communication systems. Sophisticated power control based on the joint space of channel and buffer states are essential for delaysensitive communications.