Detailed in-depth discussions covering various aspects of combinatorial chemistry such as, solid supports, linker moieties, protective groups, cleavage conditions. Furthermore, collective review of classical, as well as, recently introduced chemical transformations that applied in combinatorial synthesis combined with some recent relevant examples. Concise discussions of the physical and chemical methods utilized in the characterization and follow up of reaction progress on the solid supports. Some attention will be directed towards library design methodologies including focused and diverse designs. In depth discussion will be focused on recent advances in the area of high throughput bioassay technologies utilized to screen combinatorial libraries.