© 2015 Elsevier B.V. The application of nanoparticles has raised concern over the safety of these materials to human health and the ecosystem. After release into an aquatic environment, nanoparticles are likely to experience heteroaggregation with biocolloids, geocolloids, natural organic matter (NOM) and other types of nanoparticles. Heteroaggregation is of vital importance for determining the fate and transport of nanoparticles in aqueous phase and sediments. In this article, we review the typical cases of heteroaggregation between nanoparticles and biocolloids and/or geocolloids, mechanisms, modeling, and important indicators used to determine heteroaggregation in aqueous phase. The major mechanisms of heteroaggregation include electric force, bridging, hydrogen bonding, and chemical bonding. The modeling of heteroaggregation typically considers DLVO, X-DLVO, and fractal dimension. The major indicators for studying heteroaggregation of nanoparticles include surface charge measurements, size measurements, observation of morphology of particles and aggregates, and heteroaggregation rate determination. In the end, we summarize the research challenges and perspective for the heteroaggregation of nanoparticles, such as the determination of αhetero values and heteroaggregation rates; more accurate analytical methods instead of DLS for heteroaggregation measurements; sensitive analytical techniques to measure low concentrations of nanoparticles in heteroaggregation systems; appropriate characterization of NOM at the molecular level to understand the structures and fractionation of NOM; effects of different types, concentrations, and fractions of NOM on the heteroaggregation of nanoparticles; the quantitative adsorption and desorption of NOM onto the surface of nanoparticles and heteroaggregates; and a better understanding of the fundamental mechanisms and modeling of heteroaggregation in natural water which is a complex system containing NOM, nanoparticles, biocolloids and geocolloids.