Several groups of potentially toxic substances and their residues in animals and in animal products require constant monitoring for effective protection of human health. To properly deal with this challenge, in 1993 four institutes were designated by the European Union as community reference laboratories (CRLs) for the analysis of residues in food of animal origin, namely, RIVM in Bilthoven (The Netherlands), CNEVA-LMV in Fougères (France), BGVV in Berlin (Germany), and ISS in Rome (Italy). The functions of the four CRLs and the substances they are responsible for have been updated and listed in the annexes to Council Directive 96/23/EC (April 29, 1996). Particular emphasis is placed on that part of the activities of the CRLs aimed at promoting and supporting harmonization of approaches among national reference laboratories (NRLs). This action is achieved, among others, through coordination of research to develop new analytical methods, implementation of appropriate quality assurance schemes based on the principles of good laboratory practice, as well as on EN 45001 criteria, and, last but not least, organization of interlaboratory exercises to the benefit of the NRLs. The goal of these proficiency tests is the evaluation of the performance of each participating laboratory to improve the quality of the analytical data obtained in terms of trueness, credibility, and comparability. In the light of the mandate prescribed by Council Directive 96/23/EC the CRL at the ISS is at present responsible for the following categories of residues: (i) all chemical elements; (ii) organochlorine compounds including polychlorinated biphenyls; (iii) carbamates and pyrethroids; (iv) organophosphorous compounds. Trials of increasing difficulty are permanently conducted for the determination of organochlorine compounds, on the one hand, and As, Cd, Hg, and Pb, on the other hand. A detailed description of the two intercomparison exercises already completed for these trace elements and cursory information on the third one still in progress are given.