Strategies for multiclass, multiresidue analysis of pesticides depend on several factors that all derive from three fundamental considerations: (1) the need for the results; (2) the form and composition of the matrix; and (3) the time, resources, and technology available to the analyst. First, the need for the data dictates the quality assurance (QA)/quality control (QC) guidelines and the desired analytical figures of merit, such as limits of detection (LOD) and the accuracy and precision of the results. These needs also contribute to the choice of pesticide analytes, which sets the polarity range for the analysis. No single method can determine all pesticides in diverse matrices, so an overall strategy is often used to compartmentalize a series of approaches in order best to detect the targeted pesticides in an effective and efficient process. Second, the various types of matrices that are commonly analyzed for pesticide residues may affect the sample preparation approach employed in the analytical strategy. Common matrices for pesticide analysis consist of solids, liquids, and gases in applications associated with food, agricultural, environmental, and other sample types. Varying degrees of pesticide–matrix interactions in different materials require more or less stringent extraction procedures to separate the pesticides from the sample. Sample preparation in multiclass, multiresidue strategies frequently utilizes liquid–solid, liquid–liquid and other partitioning processes including those, such as pressurized fluid extraction (PFE), in which pressure and temperature of different fluids are controlled. Extracts often require cleanup to remove interfering co‐extracted matrix components prior to analysis. A variety of cleanup techniques based on a number of partitioning processes, such as liquid chromatography (LC), may be employed in an on‐line or off‐line fashion. Lastly, the sample extract is usually further separated and analyzed using one or more techniques. The majority of pesticides are analyzed by gas chromatography (GC) with mass spectrometry (MS) and/or element‐selective GC detectors. High‐performance liquid chromatography (HPLC) is often used in the analysis of thermally labile pesticides that are not amenable to GC analysis. Other alternatives for analysis of certain pesticide include capillary electrophoresis (CE) and immunoassays. Fundamentally, a high degree of selectivity helps in generating excellent analytical results, but the wide polarity range of analytes in multiclass, multiresidue methods (MRMs) for pesticides necessitates a great deal of effort to attain a high degree of selectivity. Trade‐offs and compromises are omnipresent in multiclass, multiresidue analysis of pesticides, and a host of strategies are available depending on how the analytical chemist prioritizes the analytical and practical considerations.