Antimicrobial resistance is a major concern for medical and agro-food industry, as frequent exposure to antimicrobial drugs/chemicals makes pathogens resistant. Bacteria in biofilms are especially resilient, as they are embedded in a protective extracellular matrix that shields them from antimicrobials. Quorum Sensing and other chemical messengers play a key role in density-dependent decision-making within large groups of microbial cells. A range of innovative experimental methodologies and procedures have been developed to explore metabolic interactions, phylogenetic connections, and competition among biofilm members. This chapter discusses the biochemistry and molecular biology of microbial biofilm formation followed by understanding how these biopolymeric microenvironment provide resistance against antimicrobial agents. Moreover, the classical and novel strategies for controlling this biofilm have been discussed. Hence, understanding this intricate relationship among similar or cross microbial species across space and time may direct novel strategies to investigate and influence microbial communities.