Development of formulations using lipid based carriers for drug delivery has been well progressed recently. However, formulation and characterization of these carriers associated with some challenges which influence drug efficacy and targeting. In addition, efficiency of these delivery systems is affected by the route they administed that is highly essential to be concidered in designing formulations. This chapter focus on the challenges faced in solid lipid nanoparticles, nanolipid carriers, liposomes and lipid drug conjugates.