textThe wireless medium is lossy due to many reasons, such as signal attenuation, multi-path propagation, and collisions. Wireless losses degrade network throughput, reliability, and latency. The goal of this dissertation is to combat wireless losses by developing effective techniques and protocols across different network layers. First, a novel opportunistic routing protocol is developed to overcome wireless losses at the network layer. Opportunistic routing protocols exploit receiver diversity to route traffic in the face of loss. A distinctive feature of the protocol is the performance derived from its optimization can be achieved in real IEEE 802.11 networks. At its heart lies a simple yet realistic model of the network that captures wireless interference, losses, traffic, and MAC-induced dependencies. Then a model-driven optimization algorithm is designed to accurately optimize the end-to-end performance, and techniques are developed to map the resulting optimization solutions to practical routing configurations. Its effectiveness is demonstrated using simulation and testbed experiments. Second, an efficient retransmission scheme (ER) is developed at the link layer for wireless networks. Instead of retransmitting lost packets in their original forms, ER codes packets lost at different destinations and uses a single retransmission to potentially recover multiple packet losses. A simple and practical protocol is developed to realize the idea, and it is evaluated using simulation and testbed experiments to demonstrate its effectiveness. Third, detailed measurement traces are collected to understand wireless losses in dynamic and mobile environments. Existing wireless drivers are modified to enable the logging and analysis of network activity under varying end-host configurations. The results indicate that mobile clients can suffer from consecutive packet losses, or burst errors. The burst errors are then analyzed in more detail to gain further insights into the problem. With these insights, recommendations for future research directions to mitigate loss in mobile environments are presented.Computer Science