Carbon nanotubes (CNTs) are widely used for biomedical applications as intracellular transporters of biomolecules owing to their ability to cross cell membranes. In this article, we survey the reported literature and results of our published work in an attempt to provide a rational view of the various CNT internalization mechanisms. Essentially three uptake mechanisms (phagocytosis, diffusion and endocytosis) have been reported in the literature. In addressing the subject of cellular internalization of CNTs, the unique physicochemical characteristics of CNTs that influence and drive the cell uptake pathway are considered. According to available evidence, the degree of dispersion, the formation of supramolecular complexes and the nanotube length are crucial factors in determining the exact mechanism of cellular uptake. In conclusion, phagocytosis appears to be the internalization pathway for CNT aggregates, bundles, cluster or single dispersed nanotubes 1 microm or more in length; endocytosis is the internalization mechanism for nanotubes forming supramolecular structures; and diffusion is the internalization mechanism for submicron CNTs that do not form supramolecular complexes. This information may be relevant to the rational design of CNT-based carriers for cell therapy.