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Identifying and quantifying relationships among landscape patterns, anthropogenic disturbances, and aquatic ecosystems is a new and rapidly developing approach to riverine ecology. In this review, we begin by describing the policy and management drivers for landscape-scale riverine research and we synthesize the technological advances that have enabled dramatic progress in the field. We then describe the development of landscape-scale riverine research through a series of landmark theoretical and review papers. Focusing on landscape-fish relationships, we consider the degree to which past efforts have been successful at meeting three challenges:(1) Has new research effectively incorporated the strengths of new technologies or are we doing the same old thing with more expensive data?(2) Have we incorporated key concepts from landscape ecology to improve our understanding of how landscapes affect rivers?(3) Have we been able to use landscape analyses to address management and policy needs? We conclude with a review of opportunities for advancement in the field of landscape-scale riverine research. These include moving toward the development of mechanistic theories of how landscapes affect rivers across disparate regions; considering the spatio-temporal structure of human impacts to landscapes; harnessing new statistical tools; and carefully defining landscape and response metrics to capture specific features.