Viral infections most often represent reactivation of latent or subclinical infection in immunocompromised host. Both viral and host factors determine the susceptibility to infection. The susceptibility and severity of viral infections increases in conditions with inherited or acquired immunodeficiency, immunosuppressive drug therapy, transplant recipients or in patients with compromised cellular immunity, e.g. HIV/AIDS. The laboratory techniques utilized for the diagnosis of viral infections include direct visualization (cytology, histology and electron microscopy), viral culture, detection of viral antigens (radioimmunoassay, enzyme immunoassay and immunofluorescence) and serological detection of antibodies. Currently molecular techniques based on the detection of viral genome are being increasingly used for the diagnosis of viral infections. In this chapter representative photomicrographs of morphological lesions identified on histopathological examination, caused by different viral pathogens in various tissues and organs under diverse clinical settings have been illustrated. A series of 8 cases of CMV infections of various organs including that of fetal CMV disease and 6 cases of post-transplant lyphoproliferative disorders (PTLD) of different organs including that of a case of post-transplant Hodgkins disease are special highlights of this chapter. Legends to each case describe the clinical presentation, radiological findings, laboratory workup and interpretation of IHC where ever indicated. Relevant references to the text have also been provided.