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Mobile multimedia applications require networks that optimally allocate resources and adapt to dynamically changing environments. Cross-layer design (CLD) is a new paradigm that addresses this challenge by optimizing communication network architectures across traditional layer boundaries. In this article we discuss the relevant technical challenges of CLD and focus on application-driven CLD for video streaming over wireless networks. We propose a cross-layer optimization strategy that jointly optimizes the application layer, data link layer, and physical layer of the protocol stack using an application-oriented objective function in order to maximize user satisfaction. In our experiments we demonstrate the performance gain achievable with this approach. We also explore the trade-off between performance gain and additional computation and communication cost introduced by cross-layer optimization. Finally, we outline future research challenges in CLD.