Despite significant improvements in early detection and refinements of therapeutic protocols over the last several decades, cancer remains one of the leading causes of death in North America. In particular, treatment of metastatic cancers is a highly desirable and yet still elusive goal of the oncologist. One strategy which holds promise is the use of self replicating viral strains with the ability to specifically kill tumour but not normal cells. These so-called “oncolytic viruses” are in general, attenuated for growth in normal cells but are able to exploit tumour specific, genetic defects to gain a growth advantage. In this review, we will discuss the virus:host cell interactions which help form the niche occupied by oncolytic viruses. The current and potential clinical applications / limitations will be discussed for oncolytic viruses from the herpesvirus, adenoviruses, picornavirus, rhabdovirus, and paramyxovirus families.