There are now available a variety of tunable solvents; these have been used extensively for extractions and in a variety of materials applications. Our focus has been to apply these techniques to chemical reactions to take advantage of the special properties available, primarily for sustainable technology, to create processes that are potentially more benign and more advantageous. We report here our work in using supercritical fluids, near-critical fluids, and gas-expanded liquids to couple organic reactions with separations. In this paper, we review applications involving improved transport, catalyst recycling, and product separation as well as the in situ generation of catalysts. Although such tunable solvents are in no way a panacea, they do offer the chemical community alternatives that can often be applied creatively to many reaction opportunities.