Cytolytic peptides are an attractive class of anticancer candidates because of their wide-spectrum lytic properties. However, their therapeutic potential cannot be realized without a proper delivery vehicle, because of their off-target toxicity, nonspecificity, and unfavorable pharmacokinetics. The physical properties of perfluorocarbon (PFC)-core surfactant-coated nanoparticles render them a highly promising delivery vehicle for targeted therapeutic applications of cytolytic peptides. This article provides an overview of the mechanism underlying the anticancer efficacy of cytolytic peptides, the limitations in clinic applications, and the advantages of PFC nanoparticles over traditional FDA-approved nanocarriers such as liposomes. Recent reports of successful anticancer therapeutics delivered by PFC nanoparticles will be discussed, as well as new applications. WIREs Nanomed Nanobiotechnol 2011 3 318-327 DOI: 10.1002/wnan.126 For further resources related to this article, please visit the WIREs website.