Biofilm is well accepted that bacteria have two life form: In planktonic form, it exists as single independent cell while in other, it manages to exist as sessile aggregates. Biofilms can tolerate nutrient shortage, pH change, reactive oxygen species, disinfectants, shear force of blood flow, phagocytes, and antibiotics. Bacterial biofilms are associated with protection from phagocytes like polymorphonuclears (PMNs) and other predators including phagotrophic protists and protozoa like free-living amoeba. This is particularly important in chronic infections where biofilms enhance recruitment of PMNs. In vivo and clinical studies on biofilms by genomic sequencing, comparative genomics, proteomics and others have shown new path of dissecting mechanism of biofilm specific resistance and of formulating antibiofilm options. New and novel strategies are being explored towards designing methods and tools to be able to reduce biofilm formation, destabilize its matrix, and/or target and kill persister cells.