Human activities in coastal and marine ecosystems provide a suite of benefits for people, but can also produce a number of stressors that can act additively, synergistically, or antagonistically to change ecosystem structure, function, and dynamics in ways that differ from single stressor responses. Scientific tools that can be used to evaluate the effects of multiple stressors are needed to assist decision making. In this paper, we review indicator selection methods and general approaches to assess indicator responses to multiple stressors and compare example ecosystem assessments. Recommendations are presented for choosing and assessing suites of indicators to characterize responses. Indicators should be chosen based upon defined criteria, conceptual models linking indicators to pressures and drivers, and defined strategic goals and ecological or management objectives. Indicators should be complementary and nonredundant, and they should integrate responses to multiple stressors and reflect the status of the ecosystem. An initial core set of indicators could include those that have been tested for the effects of climate and fishing and then expanded to include other pressures and ecosystem-specific, feature-pressure interactions. Identifying indicators and evaluating multiple stressors on marine ecosystems require a variety of approaches, such as empirical analyses, expert opinion, and model-based simulation. The goal is to identify a meaningful set of indicators that can be used to assist with the management of multiple types of human interactions with marine ecosystems.