A bioassay (in the context of natural product chemistry) is a testable system for determining the effects of a substance (or group of substances) on a living system. They can vary in complexity from simple binding assays (receptors or enzymes) to measurement of the effects on a complete organism. The natural product chemistry tradition has focused on the isolation of individual components and the assessment of their potency followed by the synthesis of the active ingredient. This reductionist approach brings a degree of control to the study of the usefulness of secondary natural products however in food systems where multiple, chronic effects are more usual, this paradigm may not operate effectively. Bioassays (particularly those which involve the use of whole organisms) can be costly and difficult to interpret so new approach methodologies (NAMs) are growing in importance. These can involve the use of cells in culture in a controlled environment. These approaches have advantages (particularly as a screening tool) and are becoming more sophisticated and relevant. The challenge of assessing complex mixtures and long-term, chronic exposure remains prevalent.