It has become increasingly evident like all other species microorganisms can also respond to environmental change and adaptation. Human beings encounter numerous severe infectious diseases, and the discovery of antibiotics was thought of as a permanent solution. However, their unregulated usage has led the organisms to attain resistance and found the treatment difficult in disease eradication. Studies in recent years had recognized the quorum sensing mechanism facilitates microorganisms, mainly bacteria, to evade from host immune response and other drugs. Quorum sensing (QS) is an intracellular communication between bacterial communities that operates through the diffusible signal molecules. These signal molecules act as an auto-inducer, which enables the bacteria to sense their population density in an environment. A variety of physiological processes such as biofilm formation, virulence expression, bioluminescence, and swarming in a range of bacterial species is regulated by QS. This contemplates the researcher's look in disrupting the signal molecule, thereby controlling disease progression. The interest in understanding the mechanism of QS signal molecules has promoted the discovery and development of numerous natural, synthetic, and semi-synthetic inhibitors for potential therapeutic applications. Most of the quorum-sensing inhibitors (QSI's) act either through quorum mimicking or quorum degradation and few studies indicate that as like antibiotic resistance (ABR), QSI's may also end up with the same fate. Thus, it is essential to understand the concept precisely to ensure that the rational drug designing of semisynthetic compounds could be safe for disease treatment with less complexity. © 2020 American Chemical Society.