Nuclear-cytoplasmic transport, which occurs through special structures called nuclear pores, is an important aspect of normal cell function, and defects in this process have been detected in many different types of cancer cells. These defects can occur in the signal-transduction pathways that regulate the transfer of factors such as p53 and β-catenin in and out of the nucleus, or in the general nuclear import and export machinery itself. In some cases, nuclear transport factors are overproduced, whereas in others, chromosomal translocations disrupt the structural proteins that make up the nuclear pore, leading to cell transformation. How does disruption of nuclear-cytoplasmic transport promote transformation, and is this process a viable therapeutic target?