The PI3K-Akt network, which is activated by cytokines or growth factors, mediates intracellular signalsto regulate a variety of cellular responses, including antiapoptosis, proliferation, cell cycling, protein synthesis, glucose metabolism, and telomere activity. Genomic mutations, alterations of the PI3K-Akt regulatorynetwork, underlie such diseases as cancer, glucose intolerance (diabetes mellitus), schizophrenia, and/orautoimmune diseases. In addition to direct tumorigenesis involvement by genetically altering human cancer, the PI3K-Akt network underlies the clinical manifestation of different stages of tumorigenic viral infection, such as latent and chronic infection, and malignant transformation of Epstein-Barr, hepatitis C, hepatitis B, and human immunodeficiency virus (HIV) viruses. We summarize updated knowledge on the PI3K-AKTnetwork underlying different phathological viral and/or bacterial infections. Antiviral activity engenderedby suppressing of PI3K-Akt activity, rather than directly targeting anticancer activity via oncogenes, maythus open up ways to prevent malignant transformation by tumorigenic viral infection.