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    ABSTRACT: The major limitation in the application of bioactive molecule is their low permeation across plasma membrane. In 1988 it was discovered, that a natural polycationic protein, the transacting activator of transcription (TAT) of the human immunodeficiency virus (HIV-1), passed very efficiently through cell membrane of cultured mammalian cells. TAT became known as the first cell penetrating peptide (CPP). CPPs have demonstrated themselves to be capable of delivering biologically active cargo to the cell interior and the vehicular capabilities of CPPs have already been harnessed for use as laboratory tools. Attached to a CPP, therapeutic cargo could be delivered to an intracellular target, thus overcoming the entry restrictions set by the plasma membrane. Since the discovery of TAT, the number of known peptides with cell-penetrating capabilities has grown and in 2003, the first CPP-based drug reached phase ɪɪ clinical trials. In this review we introduce and discuss the current knowledge of CPPs.