Ionic liquids, nanofluids, and nanomaterials have attracted great interest in the last few decades because of their extensive applications in industries, biomedical, and environmental fields. Nevertheless, their use is a cause for concern regarding their possible toxicity as well as ecological risks based on their chemical composition. Ionic liquids, which possess low volatility and tunable properties, may be cytotoxic and pose ecological hazards based on their chemical structure. Likewise, nanofluids that augment thermal conductivity in cooling systems and energy storage have toxicity risks from their nanoscale particle interactions with the biological system. Nanomaterials such as carbon-based, metal, and polymeric nanoparticles provide revolutionary opportunities in medicine, electronics, and catalysis, but their biocompatibility and long-term health implications are under investigation. This chapter gives an overview of the mechanism of toxicity of ionic liquids, nanofluids, and nanomaterials based on their physicochemical characteristics, potential for bioaccumulation, and fate in the environment. The existing methods of toxicity assessment and guidelines are also compared. The toxicological aspects of these emerging materials need to be understood to make safer alternatives and reduce the risk involved in their extensive use.