The increasing use and discharge of nanoparticles (NPs) pose risks to microorganisms that maintain the health of aquatic ecosystems. Although NPs are toxic to microorganisms, they tend to form microbial aggregates to protect themselves. Two main mechanisms account for the reduced toxicity: the dense physical structure acts as a barrier to NP exposure in the interior of the aggregate, and aggregation stabilizes a complex microbial ecosystem that enhances the ability of the community to adapt to prolonged NP exposure. We highlight the opportunities and challenges for managing microbial aggregates in wastewater treatment to remove or control NPs. For example, understanding the resistance mechanisms can help to design smart NPs that are less toxic to useful microorganisms or more toxic towards pathogenic microorganisms. NPs inevitably enter aquatic ecosystems – natural and engineered – owing to their massive use and rapid growth trend in industry and commerce. NPs come into contact with microbial aggregates, which are ubiquitous in aquatic environments. NPs exert well-known toxicities to microorganisms but, compared to planktonic cells, microorganisms in microbial aggregates are much more able to protect themselves against NPs toxicity. The dense physical structure of the aggregates acts as a barrier to NP exposure in the interior of the aggregate. Aggregation also stabilizes microbial diversity and interactions, which enhance the ability of the community to adapt to prolonged NP exposure. Because microbial aggregates are relatively good at resisting NP toxicity, their already common use in the treatment of wastewaters becomes even more beneficial when the wastewater contains NPs.