Metal-organic frameworks (MOFs—the term dates back to the late 1990s) named also porous coordination polymers are at the interface of inorganic and organic chemistry and are made up of inorganic metal nodes connected by organic moieties via coordination bonds. In this chapter, we tried to summarize the progress in using quantitative structure-activity relationships (QSAR) technique in metal-organic framework studies. QSAR methods used in MOF studies are a new and emergent area of research. In almost all papers reviewed in this area, theoretical (computational) studies are combined with experimental studies.