Infectious diseases impose serious public health burdens and often have devastating consequences. The cyclic lipopeptides elaborated by bacteria Bacillus, Paenibacillus, Pseudomonas, Streptomyces, Serratia, Propionibacterium and fungus Fusarium are very crucial in restraining the pathogens. Composed of a peptide and a fatty acyl moiety these amphiphilic metabolites exhibit broad spectrum antimicrobial effects. Among the plethora of cyclic lipopeptides, only selective few have emerged as robust antibiotics. For their functional vigor, polymyxin, daptomycin, surfactin, iturin, fengysin, paenibacterin and pseudofactin have been integrated in mainstream healthcare. Daptomycin has been a significant part of antimicrobial arsenal since the past decade. As the magnitude of drug resistance rises in unprecedented manner, the urgency of prospecting novel cyclic lipopeptides is being perceived. Intense research has revealed the implication of these bioactive compounds stretching beyond antibacterial and antifungal. Anticancer, immunomodulatory, prosthetic parts disinfection and vaccine adjuvancy are some of the validated prospects. This review discusses the emerging applications, mechanisms governing the biological actions, role of genomics in refining structure and function, semi-synthetic analog discovery, novel strain isolation, setbacks etc. Though its beyond the scope of the current topic, for holistic purpose, the role of lipopeptides in bioremediation and crop biotechnology has been briefly outlined. This updated critique is expected to galvanize innovations and diversify therapeutic recruitment of microbial lipopeptides.