Drug delivery through skin is the major confrontation due to its exceptional barrier properties. Despite major research and development efforts in transdermal systems, low Stratum corneum permeability limits the usefulness of topically administered drugs. This problem is more pronounced with bioactive drugs, which require special formulation technologies to overcome stability issues, their effective localization and safe release. This has led to an increased attention towards effective lipid based topical cutaneous systems. This review provides a brief overview of different lipid based systems, their associated advantages and disadvantages with special emphasis on lipid matrix systems like lipid microspheres or lipospheres and the potential of lipid matrix systems for transdermal delivery of bioactives.