Ecosystems are usually populated by many species. Each of these species carries the potential to show a different sensitivity towards all of the numerous chemical compounds that can be present in their environment. Since experimentally testing all possible species-chemical combinations is impossible, the ecological risk assessment of chemicals largely depends on cross-species extrapolation approaches. This review overviews currently existing cross-species extrapolation methodologies, and discusses i) how species sensitivity could be described, ii) which predictors might be useful for explaining differences in species sensitivity, and iii) which statistical considerations are important. We argue that risk assessment can benefit most from modelling approaches when sensitivity is described based on ecologically relevant and robust effects. Additionally, specific attention should be paid to heterogeneity of the training data (e.g. exposure duration, pH, temperature), since this strongly influences the reliability of the resulting models. Regarding which predictors are useful for explaining differences in species sensitivity, we review interspecies-correlation, relatedness-based, traits-based, and genomic-based extrapolation methods, describing the amount of mechanistic information the predictors contain, the amount of input data the models require, and the extent to which the different methods provide protection for ecological entities. We develop a conceptual framework, incorporating the strengths of each of the methods described. Finally, the discussion of statistical considerations reveals that regardless of the method used, statistically significant models can be found, although the usefulness, applicability, and understanding of these models varies considerably. We therefore recommend publication of scientific code along with scientific studies to simultaneously clarify modelling choices and enable elaboration on existing work. In general, this review specifies the data requirements of different cross-species extrapolation methods, aiming to make regulators and publishers more aware that access to raw- and meta-data needs to be improved to make future cross-species extrapolation efforts successful, enabling their integration into the regulatory environment. Unlabelled Image • Methods for the cross-species extrapolation of chemical sensitivity were overviewed. • Various descriptors of species sensitivity were surveyed. • Relatedness-, traits-, and genomic-predictors added mechanistic information. • An integrated framework combining approaches is suggested. • Statistical considerations important when extrapolating sensitivity are described. [ABSTRACT FROM AUTHOR]