1.1. Background Reaction and separation are the two important aspects of organic synthesis. Traditional solution-phase synthesis emphasizes reaction, while resin-based solid-phase combinatorial synthesis and polymer-assisted solution-phase parallel synthesis emphasize separation. Fluorous synthesis, which successfully integrates solution-phase reaction conditions with the phase-tag separation, has been recently introduced as a “beadless” high-speed synthetic technology.1,2 Perfluoroalkyl chains instead of resins are used as the phase tags to facilitate the separation process. Compared to traditional solution-phase and solid-phase synthesis, fluorous synthesis has the following features: Fluorous reactions have homogeneous solution-phase reaction kinetics; Fluorous molecules can be separated by the fluorous separations as well as conventional methods such as chromatography, distillation, and recrystallization; Fluorous reactions can be monitored by conventional analytical methods such as TLC, HPLC, IR and NMR; Fluorous tags are chemically stable and have minor effect on the reactivity of the attached molecules; The solubility of fluorous compounds in organic solvents can be fine-tuned by the fluorine content as well as temperature; Fluorous synthesis does not need large excess of fluorous reagents to complete the reaction; More than one fluorous reagent can be used in a single reaction; Fluorous methods are less problematic in adaptation of literature reaction conditions than that of solid-phase synthesis; Fluorous synthesis can be combined with other methods such as microwave reactions, supercritical CO2 reactions, and solid-phase synthesis; Fluorous materials can be recovered after fluorous separation. The development of fluorous technologies started in the early 1990’s. Among the pioneers, Vogt and Zhu explored the synthesis utility of temperature-dependent miscibility of fluorous solvents with organic solvents.3–4 Horvath and Rabai invented the fluorous biphasic catalysis for the recovery of catalysts.5 The Curran group and Fluorous Technologies, Inc. (FTI) developed the “light fluorous” synthesis to eliminate the use of fluorous solvents.6,7 Other major advances in fluorous technologies include mixture synthesis for making individually pure compound libraries,8 triphasic reactions which integrates the fluorous reaction and separation processes,9 and thermomorphic catalysts for fluorous solvent-free biphasic catalysis.10 Since Horvath’s seminal paper on fluorous in 1994,5 many review articles have covered different aspects of fluorous technologies at different development stages.11–27 A comprehensive and up-to-date monograph entitled “The Handbook on Fluorous Chemistry” will soon be published.28 Described in this Review are synthesis of heterocyclic systems using fluorous reagents, catalysts, scavengers, protecting groups, and tags. Application of fluorous technologies in multicomponent reactions, microwave reactions, solid-phase reactions, triphasic reactions, and mixture synthesis are also described.