Nanomaterials introduce new challenges with respect to hazard to the environment and associated risk to humans. The potential toxicity of nanomaterials may limit their applications; it is therefore important to have standardized risk hazard management guidelines and protocols to monitor their toxicity. In this chapter, common guidelines for hazard, exposure, and risk assessment of nanomaterials such as those from the Organisation for Economic Co-operation and Development (OECD), the World Health Organization, the United Nations, the International Organization for Standardization (ISO), and other such guidelines have been discussed. The OECD especially recommends that the assays and tests for nanomaterials should be adapted according to the type of nanomaterial tested. Conventional cytotoxic and genotoxic strategies available to evaluate the potential toxicity of nanomaterials in vitro and in vivo have also been discussed. Although many of the existing guidelines are suitable for the safety assessment of nanomaterials, there is scope for improvement in the OECD-recommended evaluations presently available especially so with genotoxicity.