Affinity selection-ultrafiltration/HPLC-MS is the combination of the ultrafiltration and HPLC-MS, mainly used for screening small active molecular substances from combinatorial libraries and natural product  extracts, which can bind to solution-phase targets.  Besides, it can be used in metabolic screening and     characterization of ligand-receptor binding.  It is a complement to the traditional methods of screening and identifying drugs.  This review describes its principle and application in drug study.