Almost all aspects of the discourse on the societal and environmental impacts of scientific and technological development can be framed in terms of risk and uncertainty. It is an unavoidable component of progress and innovation that some effects are unpredictable and unknown. Therefore, this topic deserves its own chapter in the context of chemical progress in science, research and design (R&D) and innovation. Here, we will shed light onto the conceptual and practical definitions of risk and uncertainty, approaches to risk assessment and risk management, the role of chemists in different risk discourse contexts, and contemporary institutional implementation of handling uncertainties in the form of the precautionary principle. Risk is one of those terms that different people associate with very different things. Chemists – that is, people with an educational background in a natural science, often working in environments in which technical problem-solving is achieved using expertise, knowledge, skills and competences – often understand risk as something empirically comprehensible (for example, the likelihood of a malfunction or contamination) or a result of ignorance that can be tackled by doing more research (that means, a cognitive challenge). We will learn that parts of the risk discourse revolve around normative and evaluative aspects. In accordance with the claims in the previous chapters, decision-makers and actors in chemistry contexts benefit from an awareness of these discourses as important contributors to an interdisciplinary endeavour: mitigating risks on a solid evidence-based factual foundation (delivered by science and empirical research) under consideration of a well-informed plausible normative framework.