Although possessing novel replicative and structural features, the family Iridoviridae has not been as extensively studied as other families of large, DNA-containing viruses (e.g., poxviridae and herpesviridae). This oversight most likely reflects the inability of iridoviruses to infect mammals and birds, and their heretofore low pathogenicity among cold-blooded animals and invertebrates. In fact, the original frog virus isolates (e.g., frog viruses 1-3) would likely have been considered orphan viruses since they were isolated from apparently healthy frogs. However, recent disease outbreaks among commercially and recreationally important fish, cultured and wild frogs, and endangered salamanders has challenged this benign view and have implicated several members of the genus Ranavirus as pathogens. This review explores three facets of ranavirus biology. In the first the salient features of ranavirus replication are summarized using frog virus 3 as a model. Secondly, criteria for characterizing new ranavirus isolates, based on biochemical (viral protein profiles, DNA restriction fragment length polymorphisms, and nucleotide sequence analysis), ecological (host range, tissue tropism), and clinical considerations, are detailed. Lastly, the principal agents of ranavirus-mediated disease and immune responses to these viruses are discussed. In light of the above, it is clear that ranaviruses are no longer orphan viruses, and that they have a significant impact on diverse populations of ectothermic animals.