Throughout the years, indiscriminate and continuous use of antibiotics has resulted in multi-resistant bacterial strains all over the world. Consequently, there is an urgent demand for an alternative to conventional antibiotics. Endogenous antimicrobial peptides hold tremendous potential in this aspect. In fact, the endogenous ‘antimicrobial peptides’, are key players of innate immunity. Two families of mammalian antimicrobial peptides have been especially well studied: defensins and cathelicidins. This manuscript describes the existence of cathelicidin peptide in buffalo (Bubalus bubalis) and identifies two novel members of cathelicidin family in this species. This book will act as guiding force for the research community to unravel the role of cathelicidin peptide in immune defence mechanism of buffalo, which is well known for its disease resistance capacity. It may also arouse biological as well as commercial interest in endogenous cationic peptides as potential antimicrobial therapeutics to combat the problem of bacterial antibiotic resistance in near future.