Environmental health indicators (EHIs) are applied in a variety of research and decision-making settings to gauge the health consequences of environmental hazards, to summarize complex information, or to compare policy impacts across locations or time periods. While EHIs can provide a useful means of conveying information, they also can be misused. Additional research is needed to help researchers and policy-makers understand categories of indicators and their appropriate application. In this article, we review current frameworks for environmental health indicators and discuss the advantages and limitations of various forms. A case study EHI system was developed for air pollution and health for urban Latin American centers in order to explore how underlying assumptions affect indicator results. Sixteen cities were ranked according to five indicators that considered: population exposed, children exposed, comparison to health-based guidelines, and overall PM10 levels. Results indicate that although some overall patterns in rankings were observed, cities’ relative rankings were highly dependent on the indicator used. In fact, a city that was ranked best under one indicator was ranked worst with another. The sensitivity of rankings, even when considering a simple case of a single pollutant, highlights the need for clear understanding of EHIs and how they may be affected by underlying assumptions. Careful consideration should be given to the purpose, assumptions, and limitations of EHIs used individually or in combination in order to minimize misinterpretation of their implications and enhance their usefulness.