Members of the genus Orthoreovirus in the family Reoviridae are nonenveloped, icosahedral viruses. Their genomes contain 10 segments of double-stranded RNA (dsRNA). The orthoreoviruses are divided into two subgroups, the fusogenic and nonfusogenic reoviruses, based on the ability of the virus to induce cell-to-cell fusion. The fusogenic subgroup consists of the avian reovirus, baboon reovirus, pteropine reovirus, and reptilian reovirus, whereas the nonfusogenic subgroup consists of the prototypical mammalian reovirus (MRV) species. MRVs are highly tractable experimental models for studies of segmented dsRNA virus replication and pathogenesis. Moreover, MRVs can selectively kill tumor cells and have been evaluated as oncolytic agents in clinical trials. This review provides a brief overview of current knowledge on the virological features of MRVs.