This review provides an introduction to three of the most well-developed solvent replacement strategies currently under investigation for synthetic chemistry: Ionic liquids, fluorous phase techniques, and supercritical carbon dioxide. They are all fascinating reaction media, and have considerable potential for use in pharmaceutical synthesis. However, this has to be balanced with problems and limitations of the new methods. This review aims to provide an overall account of recent advances in the use of unusual media for synthetic chemistry, with an emphasis on highlighting potential benefits, but also limitations, of each of the methods described.