Liquid-phase combinatorial library synthesis is commonly developed into the viable alternatives or adjunct across the broad spectrum of polymer-supported organic chemistry. It includes the use of soluble polymer supports in the combinatorial synthesis of peptides and small-molecular library compounds which act as catalyst and reagent supports. It also includes high throughput biological screening with generation and evaluation of chemical leads for drug discovery development. In this review, liquid-phase combinatorial library synthesis is shown as the most efficient method of choice for the synthesis of most of the combinatorial library compounds with specific approaches from different groups that state potentials of solution-phase combinatorial synthesis.