‘De minimis risk’ is a basic concept and principle of risk analysis, which states that risks which are sufficiently small can be ignored. This principle is commonly used in practical risk analysis and related decision-making, but its rationale is debated. Recently, authors have argued that de minimis reasoning has no place in rational decision-making. The present paper provides a perspective on the foundation and use of this principle in a risk analysis context. The main aim of the paper is to gain new knowledge about the meaning and scope of the principle in view of contemporary risk science. We evaluate the extent to which different perspectives on risk can explain the disputes concerning the suitability of the principle. Current discussions of the principle have to a large extent been based on probabilistic-based frameworks, whereas the present study also addresses uncertainty-based risk perspectives. Examples are used to illustrate the discussion.