Currently, the World Health Organization (WHO) considers antibiotic resistance a serious threat to the treatment of infectious diseases. Moreover, the WHO has promoted a complex action plan, based on the slogan “no action today, no cure tomorrow” to control the occurrence and spread of resistant strains that include strategic actions for mitigation, prevention and control. In the last 50 years, only three new classes of antibiotics have been approved by WHO and US Food and Drug Administration (FDA), among which the third one was only approved this year and found to be effective against the Gram-negative Enterobacteriaceae group for the first time after 1962. Keeping all the above facts of continuous emergence of antibiotic resistance in planktonic bacteria and in their biofilm counterpart, this book chapter has tried to add some more alternative drug resources by means of natural products, which could ultimately lead to the betterment of humankind. Several recent studies have shown that natural products (mainly phytochemicals) exhibit their antibacterial activity through different mechanisms of action like bacterial membrane damage, inhibition of virulence factors, quorum sensing signalling, inhibition of enzymes and toxins. Quorum sensing is a signalling process to regulate the expression of several virulence factors in both Gram-negative and Gram-positive bacteria via an autoinducing loop. When a critical bacterial cell density is reached, a complex of the regulatory proteins and specific signalling molecules enable the autoinduction of the quorum sensor and the expression of the target genes. Quorum sensing inhibitors (QSIs) interfering with this regulatory network have either been derived from natural sources viz. phytochemicals and fungi, or they have been chemically synthesized. In this chapter, we will summarize the updates from the available literature describing the various QSIs obtained from natural sources and their role as anti-infective agents. We will also discuss the feasibility of these sources towards the development of future drugs to cure systematic infections in the human body.