Risk has been defined by the World Health Organization International Program on Chemical Safety as "the probability of an adverse effect in an organism, system or (sub) population caused under specified circumstances by exposure to an agent". This article addresses some of the key components of this definition. Determining risk is dependent on expert judgement of the overall body of evidence relating to adverse effects or hazards. Such evidence can come from a range of experimental and observational studies and reports. Ideally determining risk to humans would be based upon evidence from humans rather than from experimental animals but this is generally not feasible. Even when epidemiological studies are available there can be difficulties in ascribing a disease to a causal chemical agent, and there are inevitable limitations in assessing exposure. Whilst probability refers to a mathematical or statistical quantification of the proportion of a population at risk of adverse effects, it is more common to compare point estimates of exposure with health-based guidance values.