The interest in polynucleotide translocation through nanopores has moved from purely biological to the need of realizing nanobiotechnological applications related to personalized genome sequencing. Polynucleotide translocation is a process in which biomolecules, like DNA or RNA, are electrophoretically driven through a narrow pore and their passage can be monitored by the change in the ionic current through the pore. Such a translocation process, which will be described here offers a very promising technology aiming at ultra-fast low-cost sequencing of DNA, though its realization is still confronted with challenges and drawbacks. In this review, we present the main aspects involved in the polynucleotide translocation through solid-state nanopores by discussing the most relevant experimental, theoretical, and computational approaches and the way these can supplement each other. The discussion will expose the goals that have been reached so far, the open questions, and contains an outlook to the future of nanopore sequencing. (C) 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 985-1011, 2011