Indirect effects in ecotoxicology are defined as chemical- or pollutant-induced alterations in the density or behavior of sensitive species that have cascading effects on tolerant species in natural systems. As a result, species interaction networks (e.g., interactions associated with predation or competition) may be altered in such a way as to bring about large changes in populations and/or communities that may further cascade to disrupt ecosystem function and services. Field studies and experimental outcomes as well as models indicate that indirect effects are most likely to occur in communities in which the strength of interactions and the sensitivity to contaminants differ markedly among species, and that indirect effects will vary over space and time as species composition, trophic structure, and environmental factors vary. However, knowledge of indirect effects is essential to improve understanding of the potential for chemical harm in natural systems. For example, indirect effects may confound laboratory-based ecological risk assessment by enhancing, masking, or spuriously indicating the direct effect of chemical contaminants. Progress to better anticipate and interpret the significance of indirect effects will be made as monitoring programs and long-term ecological research are conducted that facilitate critical experimental field and mesocosm investigations, and as chemical transport and fate models, individual-based direct effects models, and ecosystem/food web models continue to be improved and become better integrated.