Analysis of virus-host interactions has revealed a variety of ways in which viruses utilize and/or alter host functions in an effort to facilitate efficient replication. Recent work has suggested that certain RNA viruses that replicate in the cytoplasm disrupt the normal trafficking of cellular RNAs and proteins within the host cell. This review will examine the recent evidence showing that poliovirus and vesicular stomatitis virus (VSV) can inhibit nucleo-cytoplasmic transport within cells. Interestingly, the data indicate that inhibition by both viruses involves targeting components of the nuclear pore complex (NPC). Following this, several possible explanations for why viruses might disrupt nucleo-cytoplasmic transport are discussed. Finally, the possibility that disruption of nucleo-cytoplasmic trafficking may be a more common feature of RNA virus-host interactions than previously thought is examined.