Great advances have been made in the past five decades in understanding the molecular mechanics of the two-component signal transduction pathway in bacteria but its applications in Medicine and Food Industries are yet to be fully unravelled. We discuss the varying changes in the extracellular environment of bacteria and their possession of multiple Two-Component Systems with each being specialize to react to a specific environmental signal, such as pH, nutrient level, redox state, osmotic pressure, quorum signals, and antibiotics. The sensitivity of this response transmits information between different Two-Component Systems to form a complex signal transduction network. Bacteria’s signal transduction system, referred to as a two-component system, are essential for adaptation to external stimuli. These systems provides a signal transduction pathways widely employed from prokaryotes to eukaryotes. Typically, each two-component system composed of a sensor protein distinctively monitors an external signal(s) and a response regulator (RR) that controls gene expression and other physiological activities which are collectively assembled in a signal transduction pathway. This annex reviews the molecular mechanics underlying the signal transduction systems in prokaryotic organisms. It is not uncommon to hear, either explicitly or implicitly, the statement that “two component regulatory systems are well understood”. Therefore, we examine the current models of the mechanisms of the regulatory systems and provide viable suggestions to further expand its applications in drug efficiency and antibiotic resistance in humans as well as enhancing the shelf-life of products in the food industry. We also outline the challenges that might have quenched possible trials of this application to human health.