A major thrust in the biomedical and pharmaceutical industries is to develop diagnostic and therapeutic tools that have significantly improved selectivity and specificity compared to the current state-of-the-art. This has driven much of the effort to look at molecules and materials that are significantly larger than the traditional small molecule agents. Due to size restrictions, however, many of these materials are unable to penetrate the cell membrane and gain access to the intracellular components on which they exert their action. The relatively recent discovery of cell penetrating peptides (CPP) provides a powerful tool that has enabled the intracellular delivery of these materials. While a variety of proteins, DNA, polymers and even nanoparticles have been successfully delivered into cells, there still remains some debate as to the mechanism of entry utilized by the CPPs. In this review, we provide a brief outline of the different potential mechanisms for cellular uptake of CPPs.