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.