Many studies have shown that streams degrade in response to urbanization in the watershed. These studies often are based on use of biotic and abiotic variables to measure stream health across a gradient of land cover/land use. The results of these studies can be applied to other urban systems, but often fail to provide a mechanistic understanding of the urban impact, in part, because of the nature of the experimental design. We analyzed the advantages and disadvantages of using environmental gradient studies to further understanding of urban stream systems. We also evaluated alternative experimental design approaches, including best management practice monitoring, long-term watershed studies, paired-watershed studies, and before–after control–impact studies, which could be used to complement the gradient approach. We illustrate these theoretical discussions with an urban paired-watershed case study in the Etowah watershed in northern Georgia. Our goal is to move experimental designs in a direction that will further our mechanistic understanding of the effects of existing urbanization on aquatic ecosystems and will provide opportunities to evaluate stream responses to environmentally sensitive urban land cover.