The introduction of combinatorial chemistry and the development of high-throughput techniques has significantly increased the amount of new active lipophilic molecular entities. As a result, the need for successful delivery of these lipophilic active compounds has also increased. One such method of delivery is through the use of advanced lipid-based drug delivery systems. Traditionally, the majority of reviews of lipid-based drug delivery systems were based on the oral administration field only. This review article focuses on the use of lipids in parenteral, dermal/ transdermal, and ocular drug delivery systems. Specific needs, considerations, approaches, and limitations in lipid-based drug delivery are discussed herein on the basis of the anatomical and physiological diversity of the target organs and systems.