Especially living tissues, implants, catheters, pacemakers, prosthetic heart valves, composite resins, glass ionomer cements, chronic wounds, contact lenses and ceramic materials, etc. It has now been proven that bacteria on all surfaces live a micro-social lifestyle by using Quorum Sensing System (QS), communicating through N-Acyl Homoserine Lactone (AHL) signaling molecules, and forming biofilm layer, which is one of most vital virulence factors. In 1978, with discussions of Robert Koch's hypotheses published in 1884, Bill Costerton warned about magnitude of biofilm damage in chronic infections. In 2012, Father of biofilm Bill Costerton broke new ground in his research on biofilm. The concept of "Cell-to-cell communication", which Smith first brought to agenda in 1905, has brought infectious diseases to huge scientific level with QS system and biofilm, which is most important virulence factor of this system. Within the biofilms, bacteria can easily reproduce and communicate with each other, there’s actually a fiber optic system that bacteria communicate with each other at speed of light, QS. Biofilm was defined as a ‘City of Microbes’ by Watnick and Kolter, (2000). Biofilm is mixture of different microorganisms that are held together and protected by glue-like film. It’s a slimy matrix and coating that bacteria, fungi, yeast, mold, mycotoxins, viruses and parasites create in order to stay protected and elude immun system. A dysregulated nervous system can lead to taxed immune system. This layer of glue-like slime creates a protective ‘sleeping bag’ for bacteria, so they can continue to do what they do best, which is thriving in you, while creating chronic diseases. The immune system fully recognizes bacteria, however, can’t get to them due to the protective layer as biofilm, thus many times creating an autoimmune situation or cannot effective. In summary, understanding of biofilm is vital to manage and to eradicate biofilm-related diseases. The current review is, therefore, an effort to encompass the current concepts in biofilm, biofilm architectural and its implications in all living creature health and disease.