Considerable adverse side effects and cytotoxicity of highly potent drugs for healthy tissue require the development of novel drug delivery systems to improve pharmacokinetics and result in selective distribution of the loaded agent. The introduction of targeted liposomal formulations has provided potential solutions for improved drug delivery to cancer cells, penetrating delivery through blood–brain barrier and gene therapy. A large number of investigations have been developed over the past few decades to overcome pharmacokinetics and unfavorable side effects limitations. These improvements have enabled targeted liposome to meet criteria for successful and improved potent drug targeting. Promising in vitro and in vivo results for liposomal-directed delivery systems appear to be effective for vast variety of highly potent therapeutics. This review will focus on the past decade’s potential use and study of highly potent drugs using targeted liposomes.