Abstract: Protein structure similarity comparison is one of the research hotspots in modern bioinformatics.In recent years,many methods were proposed which are capable of comparing all available protein structures.Neverthe less,difficulties still exist in interpreting the results of the se comparisons.In this paper,we sort all the current methods into geometry based,topology based and statistics based approaches,and investigate the ir merits in 3D protein structure similarity analysis.Finally,we highlight the future research directions in this field.