In Japan, the Positive List System for the regulation of agricultural chemical residues in foods has been in force since May 29, 2006. Moreover, food poisoning caused by methamidophos-laced frozen gyōza dumplings came to light on Jan. 30, 2008. The news has set off alarms about the safety of not only perishables but also unexpected pesticides in processed foods. Therefore, a reliable systematic method was developed for determining pesticide residues in various foods. Firstly, ca. 200 target pesticides were selected by statistically analyzing the monitoring data in Aichi Prefecture. Secondly, a systematic method using plural separation and detection systems combining GC-MS/MS and LC-MS/MS as first priority was constructed. As the sample preparation method corresponding to the systematic method, a simple and easy acetonitrile extraction method, an auto-cleanup system combining GPC and mini-column SPE were developed. Thirdly, a new official multi-residue method that is able to determine a wide range of pesticides in various foods including fatty processed foods was developed. And finally, a comprehensive chromatographic detection system by dual-column GC-MS(/MS) and an interactive database without the use of pesticide standards was commercialized.