Extrusion reactions may be defined as chemical reactions in which an atom or small molecular fragment Y connected to two other atoms W and Z is lost from a molecule, leading to a product in which W becomes directly bonded to Z. Cheletropic reactions that afford aromatic or conjugated π systems by loss of a stable atomic or molecular fragment have also been classified as extrusion reactions. Typically, the fragments liberated in these reactions are small, stable inorganic molecules or atoms such as carbon monoxide, carbon dioxide, sulfur, sulfur monoxide, sulfur dioxide, selenium, tellurium, oxygen and nitrogen. This chapter primarily deals with the synthesis of arenes, heterocycles, 1,3-dienes and polyenes using such extrusion processes. The utility of these reactions in the synthesis of sterically hindered molecules, dendrimers, pheromones, and other natural products are highlighted. The use of extrusion reactions for the “Click and Release” approach in drug development is also introduced.