This chapter surveys the problem of the lack of experimental physico-chemical and toxicity data for chemicals in the environment. The need for the new legislation of chemicals, REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), and the utility of QSAR models in this context are highlighted. The reliability and success of QSAR models for environmental properties is discussed, with emphasis on all the crucial problems, such as quality of input data, molecular descriptors, modelling methods, applicability domain, validation tools and descriptorsâ meaning. The discussion on these points has been organized according to the OECD Principles for the Validation, for Regulatory Purposes, of (Q)SAR Models. The utility of models for cumulative end-points (POPs, PBTs, etc.) for the screening and prioritization of environmental chemicals and for the design of safer alternative compounds is also presented.