is an opportunistic pathogen that synthesizes and secretes a wide range of virulence factors. poses a potential threat to human health worldwide due to its omnipresent nature, robust host accumulation, high virulence, and significant resistance to multiple antibiotics. The pathogenicity of , which is associated with acute and chronic infections, is linked with multiple virulence factors and associated secretion systems, such as the ability to form and utilize a biofilm, pili, flagella, alginate, pyocyanin, proteases, and toxins. Two-component systems (TCSs) of perform an essential role in controlling virulence factors in response to internal and external stimuli. Therefore, understanding the mechanism of TCSs to perceive and respond to signals from the environment and control the production of virulence factors during infection is essential to understanding the diseases caused by infection and further develop new antibiotics to treat this pathogen. This review discusses the important virulence factors of and the understanding of their regulation through TCSs by focusing on biofilm, motility, pyocyanin, and cytotoxins.