Abstract Today’s nanotechnologies can substantially improve the properties of a wide range of products in all sectors of activity, from the manufacture of materials with ground-breaking performance to medical diagnostics and treatment—yet they raise major technological, economic, ethical, social and environmental questions. Some of the spinoffs we can expect include the emergence of new markets, job creation, improvements in quality of life and contributions to protection of the environment. The impact of nanotechnologies is already being felt in sectors as diverse as agroprocessing, cosmetics, construction, healthcare and the aerospace industry. Most universities in Québec and many research centres are working to design new applications. Many companies have projects in the start-up phase, while others are already producing nanomaterials or have incorporated them in their processes to improve product performance, a trend expected to accelerate over the coming years. These new developments, which could mean exposure of a growing number of workers to these infinitesimally small particles, are of particular concern to workers in industry and staff in research laboratories. It is estimated that in 2015 about 10% of manufacturing jobs worldwide will be associated with nanotechnologies, and more than 2,000 commercial products will contain nanomaterials. Given our fragmentary knowledge of the health and safety risks for workers and the environment, the handling of these new materials with their unique properties raises many questions and concerns. In fact, many studies have already demonstrated that the toxicity of certain nanomaterials differs from that of their bulk counterparts of the same chemical composition. Nanomaterials enter the body mainly through inhalation but also through the skin and the GI tract. Animal studies have demonstrated that certain nanomaterials can enter the blood stream through translocation and accumulate in different organs. Animal studies also show that certain nanomaterials cause more inflammation and more lung tumours on a mass-for-mass basis than the same substances in bulk form, among many other specific effects documented. In addition, research has shown that the physicochemical characteristics of nanomaterials (size, shape, specific surface area, charge, solubility and surface properties) play a major role in their impact on biological systems, including their ability to generate oxidative stress. It is thus crucial that risks be assessed and controlled to ensure the safe handling of nanomaterials. As with many other chemicals, a risk assessment and management approach must be developed on a case-by-case basis. There is still no consensus, however, on a measurement method for characterizing occupational exposure to nanomaterials, making quantitative risk assessment difficult if not impossible in many situations. As a result, a precautionary approach is recommended to minimize worker exposure. In Québec, the employer is responsible for providing a safe work environment, and preventive measures must be applied by employees. Accordingly, preventive programs that take into account the specific characteristics of nanomaterials must be developed in all work environments where nanomaterials are handled, so that good work practices can be established and preventive procedures tailored to the risks of the particular work situation can be introduced. Fortunately, current scientific knowledge, though partial, makes it possible to identify, assess and effectively manage these risks. This best practices guide is meant to support the safe development of nanotechnologies in Québec by bringing together current scientific knowledge on hazard identification, strategies for determining nanomaterial levels in different work environments, risk assessment and the application of various risk management approaches. Some knowledge of occupational hygiene is required to use this guide effectively. Designed for all work environments that manufacture or use nanomaterials, this guide provides practical information and prevention tools for the safe handling of nanomaterials in laboratories and pilot plants as well as industrial facilities that produce or incorporate them. To be effective, risk management must be an integral part of an organization’s culture, and health and safety issues must be considered when designing the workplace or as far upstream as possible. This is crucial for good organizational governance. In practice, risk management is an iterative process implemented as part of a structured approach that fosters continuous improvement in decision-making and can even promote better performance. The purpose of this guide is to contribute to the implementation of such an approach to the prevention of nanomaterial-related risks only. Depending on the process, other risks (associated with exposure to solvents, gas, heat stress, ergonomic stress, etc.) may be present, but they are not addressed in this guide. The authors recommend a preventive approach designed to minimize occupational exposure to nanomaterials. Given the different exposure pathways, the many factors that can affect nanomaterial toxicity and the health risks, our approach is essentially based on hazard identification, different risk assessment strategies and a hierarchy of control measures, incorporating knowledge specific to nanomaterials when available. Risk assessment makes it possible to select processes, equipment and work methods that reduce occupational exposure, in particular by controlling nanomaterial emissions at the source. It also makes it possible to select collective and individual preventive measures and to determine administrative management measures and training needed to protect all workers—operators as well as those who maintain equipment and workspaces. This second edition incorporates new information in the scientific literature. In addition, appendices have been included describing initiatives in Québec workplaces; examples of at-risk situations described in the literature; preventive measures and data on their relative efficacy; and the implementation of measures to control exposure. Finally, we note that solutions for any particular workplace must be developed on a case-by-case basis taking into account the risk assessment of each workstation.