Reovirus has an inherent preference for replicating in cells with dysregulated growth factor signaling cascades that comprise Ras activation. Precisely how reovirus exploits the host cell Ras pathway is unclear, but there is evidence suggesting that activated Ras signaling is important for efficient viral protein synthesis. Defining the molecular mechanism of reovirus oncolysis will shed light on reovirus replication and important aspects of cellular transformation, Ras signaling cascades and regulation of protein translation.