A comprehensive review is presented on the recent developments and trends in the QuEChERS (quick, easy, cheap, effective, rugged, and safe) sample preparation approach. This technique involves liquid-liquid partitioning using acetonitrile and purifying the extract using dispersive solid-phase extraction (d-SPE). Originally, the QuEChERS was introduced for pesticides residues analysis in high moisture fruits and vegetables, but more recently it is gaining significant popularity in the analysis of broad spectrum of analytes in huge variety of samples. The wide range of the technique applications is possible due to introducing various modifications based on the use of different extraction solvent and salt formulation and buffer additions for salting-out partitioning step and the application of various d-SPE sorbents for clean-up step. Therefore, the QuEChERS approach is useful for analysis of, among others pesticides, veterinary drugs and other pharmaceuticals, mycotoxins, polycyclic aromatic hydrocarbons (PAHs), dyes, acrylamide, synthetic musks and UV filters, bisphenols, polybrominated diphenyl ethers and other flame retardants, endocrine disruptors, and other chemical compounds. Thanks to the QuEChERS approach, high-throughput multiresidue methods operate in a routine contaminant control of food products, feedstuff, and environmental samples.