Pathogen is defined as any organism capable of causing disease whereas pathogenicity is the ability of an organism to produce disease. In this context, disease is a definitive morbid process having a characteristic set of symptoms. Furthermore, disease may affect the whole organism or any of its component cells or tissues. Regardless of the etiology, disease may either be clinically apparent or subclinical; and the outcome is dependent on the pathogen, the properties of the host, and the environment where they reside. For example, the virulence of infectious hematopoietic necrosis virus (IHNV) may vary with the age, species, and life stage of salmonid fish and water quality parameters including temperature. This review describes factors affecting the virulence of IHNV for salmonid fish and how these factors are involved in the host–pathogen–environment interaction that determines occurrence of disease.