Cancer is a complex disease that often eludes successful treatment due to its propensity to evolve or adapt in the face of current therapeutic regimes. It is reasonable to suggest that sophisticated therapeutics that can attack cancers in multiple, but targeted ways, will be necessary in order to improve current success rates. It is the thesis of this article that Oncolytic Viruses (OVs), are a new generation of “smart therapeutics” for cancer with tremendous potential to revolutionize the management of what has become one of mankinds scourges. A number of viruses are being developed around the world for this purpose (one has already been approved for human use in China ) and I propose that it is now essential to embrace the technology and use our recent and evolving understanding of the molecular biology of cancer to fully exploit the oncolytic virus platform. In the remainder of this article I speculate on some of the next important steps in OV development and directions the platform may be headed in the future.