I. Introduction 45 II. Pesticide Structures and Properties 46 III. Extraction and Isolation Methods from Environmental and Food Samples 47 IV. LC/MS/MS Analysis of Pesticides 53 A. Interfacing Systems 53 B. Instrumental Aspects 57 C. Optimization of Chromatographic Mass Spectrometric Conditions 57 V. Tandem MS Methods 59 A. Triple Quadrupole 59 B. Quadrupole Ion Trap 66 C. Hybrid Quadrupole TOF (Q‐TOF) 71 VI. Performance Characteristics of LC‐Tandem MS for Pesticides 72 VII. Applications 75 VIII. Conclusions 80 References 81 An overview is given on pesticide‐residue determination in environmental and food samples by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Pesticides comprise a large number of substances that belong to many completely different chemical groups, the only common characteristic is that they are effective against pests. They still constitute a challenge in MS because there is no collective pathway for fragmentation. A brief introduction to the theory of tandem MS permits a discussion of which parameters influence the ionization efficiency when the ions are subjected to different actions. Emphasis is placed on the different tandem MS instruments: triple and ion‐trap quadrupoles, and hybrid quadrupole time‐of‐flight (Q‐TOF), including advantages and drawbacks, typical detection limits, and ion signals at low concentrations. The instrumental setup, as well as LC and mass spectrometric experimental conditions, must be carefully selected to increase the performance of the analytical system. The capacity of each instrument to provide useful data for the identification of pesticides, and the possibility to obtain structural information for the identification of target and non‐target compounds, are discussed. Finally, sample preparation techniques and examples of applications are debated to reveal the potential of the current state‐of‐the‐art technology, and to further promote the usefulness of tandem MS. © 2003 Wiley Periodicals, Inc., Mass Spec Rev 23:45–85, 2004