This landscape and predictive tools methods manual, developed collaboratively by U.S. EPAs Office of Water, Office of Research and Development, Regional Offices and others, describes the purpose, rationale, and basic steps for using landscape and predictive tools for Clean Water Act monitoring, assessment and management purposes. Landscape and predictive tools are needed both to guide efficient filling of monitoring gaps and to prioritize our protection and rehabilitation actions. This should yield better protection for high quality waters and quicker, more cost-effective restoration of impaired waters. We have organized this method guidance document into four sections: (I) Introduction to Landscape and Predictive Tools; (II) Geographic Frameworks, Spatial Data, and Analysis Tools; (III) Examples and Case Studies; and (IV) Gaps and Needs for Research and Applications. In addition, the extensive Toolbox provides links to and short descriptions of a wide range of easily accessed data sets and analytical tools. This guidance stresses simultaneous use of matched (or paired) landscape and in situ data for empirical modeling to enhance our predictive capabilities and encourage science-based targeting and priority setting. Landscape and predictive tools have a wide range of current and potential applications including criteria and standards development, problem identification and prevention, prioritization and targeting of rehabilitation, and advancing science, education, and societys ability to effectively manage aquatic and terrestrial resources.