Natural antimicrobial peptides have been shown as one of the important tools to combat certain pathogens and play important role as a part of innate immune system in plants and, also adaptive immunity in animals. Defensin is one of the antimicrobial peptides with a diverse nature of mechanism against different pathogens like viruses, bacteria and fungi. They have a broad function in humans, vertebrates, invertebrates, insects, and plants. Plant defensins primarily interact with membrane lipids for their biological activity. Several antimicrobial peptides (AMPs) have been overexpressed in plants for enhanced disease protection. The plants defensin peptides have been efficiently employed as an effective strategy for control of diseases in plants. They can be successfully integrated in plants genome along with some other peptide genes in order to produce transgenic crops for enhanced disease resistance. This review summarizes plant defensins, their expression in plants and enhanced disease resistance potential against phytopathogens.