Assessment of ecological integrity is the basis for sustainable management of the ecosystem services lakes provide. Periphyton is used in stream assessment, but lake assessment is based mostly on water-column variables. We addressed the use of periphyton to assess lakes, how factors influence responses of periphyton metrics, and whether periphyton provides unique information for determining biological condition and identifying risks. Much effort directed at using periphyton for assessment has focused on linear relationships between taxonomic metrics and single stressors. These relationships can be good proxies for water chemistry, but do not always represent biological conditions. Community diversity is difficult to relate to stressors because low values may result from natural conditions (grazing, disturbance). Quantile regression, River Invertebrate Prediction and Classification System (RIVPACS)-type models, and taxonomic distinctiveness may provide more precise indicators. Periphyton biomass and productivity are linked closely to trophic status but are rarely used in assessment. Responses of these variables over a trophic gradient are often nonlinear, and surrogate metrics that use quantile regression or weighted-averaging calibration/regression based on community composition may overcome this problem for assessment. Measures, such as alkaline phosphatase activity, number of N-fixing taxa, and periphyton nutrient stoichiometry can be used to assess littoral-zone ecosystem function and to help establish causative effects of stressors. The value added by periphyton-based assessment is that it provides higher-level understanding of the ecological status of the littoral zone. Assessment must be rooted in a strong understanding of the science and must provide guidance and cost-effective options for lake managers. We outline a hierarchy for periphyton assessment methods that assess risk at different levels of effort and precision.