Bacterial enzyme ÂÂÂHyaluronidaseÂÂÂ is a complex polysaccharide degrading enzyme that cleaves â-GlcNAc-(1ïÂÂ®4) glycosidic linkage of Hyaluronate (HA) by â-elimination process. It is synthesized by a spectrum of grampositive bacteria which serve as potential contributors to a multitude of infectious diseases in human beings. Especially, group A streptococcus bacteria (GAS) have evolved several orders of magnitude to attack the host organism and establish infection. Hyaluronidase led pathogenic/ infectious cycle is accomplished through a cascade of events where an escape fromthe hostÂÂÂs immunity is very important. In this regard, a variety of factors are utilized by hyaluronidases which determine the successful bacterial penetration into hosts, like the use of substrate HAand/or itÂÂÂs enveloping capsule as energy source during HA lysis, genetic variation among the bacterial strains in the form of allelic polymorphisms, hyaluronidase enzyme structure-driven substrate binding properties etc. Previous studies have furnished better insights on nucleotide sequences of hyaluronidase genes and immunopathogenesis. However, for a better understanding of hyaluronidase association with bacteria and overall host-pathogen interaction, much investigation and literature support is still needed.