�We are currently witnessing a rapid growth of interest in nanotech applications for medicine, most of them focused on radical improvements of current therapies and diagnostic modalities. After a real boom in the development of novel micro- and nano-sized particulate drug delivery systems (DDS) in academic laboratories and pharmaceutical companies all over the world; however, we have now reached the point when the first ‘reality check’ can be made and the many limits and shortcomings of existing DDS can be evaluated. The major effect of drug administration in loaded DDS can be determined as a principal change in drug pharmacokinetics and bioavailability. Many current DDS have been developed with the aim of reducing biodegradation or in vivo toxicity of drugs. Others have focused on increasing bioavailability, cell-selective accumulation, or activity of encapsulated drugs after administration. Initial generations of DDS were optimized in cell cultures by modifications of the chemical structure or physicochemical properties in order to effectively modulate cellular drug accumulation, release kinetics and overall therapeutic effect.