There has been a surge of consumer products that incorporate nanoparticles, which are used to improve or impart new functionalities to the products based on their unique physicochemical properties. With such an increase in products containing nanomaterials, there is a need to understand their potential impacts on the environment. This is often done using various biological models that are abundant in the different environmental compartments where the nanomaterials may end up after use. Beyond studying whether nanomaterials simply kill an organism, the molecular mechanisms by which nanoparticles exhibit toxicity have been extensively studied. Some of the main mechanisms include (1) direct nanoparticle association with an organism's cell surface, where the membrane can be damaged or initiate internal signaling pathways that damage the cell, (2) dissolution of the material, releasing toxic ions that impact the organism, generally through impairing important enzyme functions or through direct interaction with a cell's DNA, and (3) the generation of reactive oxygen species and subsequent oxidative stress on an organism, which can also damage important enzymes or an organism's genetic material. This Account reviews these toxicity mechanisms, presenting examples for each with different types of nanomaterials. Understanding the mechanism of nanoparticle toxicity will inform efforts to redesign nanoparticles with reduced environmental impact. The redesign strategies will need to be chosen based on the major mode of toxicity, but also considering what changes can be made to the nanomaterial without impacting its ability to perform in its intended application. To reduce interactions with the cell surface, nanomaterials can be designed to have a negative surface charge, use ligands such as polyethylene glycol that reduce protein binding, or have a morphology that discourages binding with a cell surface. To reduce the nanoparticle dissolution to toxic ions, the toxic species can be replaced with less toxic elements that have similar properties, the nanoparticle can be capped with a shell material, the morphology of the nanoparticle can be chosen to minimize surface area and thus minimize dissolution, or a chelating agent can be co-introduced or functionalized onto the nanomaterial's surface. To reduce the production of reactive oxygen species, the band gap of the material can be tuned either by using different elements or by doping, a shell layer can be added to inhibit direct contact with the core, or antioxidant molecules can be tethered to the nanoparticle surface. When redesigning nanoparticles, it will be important to test that the redesign strategy actually reduces toxicity to organisms from relevant environmental compartments. It is also necessary to confirm that the nanomaterial still demonstrates the critical physicochemical properties that inspired its inclusion in a product or device.