Interferon-gamma (IFN-γ) is a key immunoregulatory protein that plays a major role in the host innate and adaptive immune response. Also known as type II interferon, IFN-γ is a single-copy gene whose expression is regulated at multiple levels by the host. Transcription control is regulated through epigenetic mechanisms as well as the accessibility of chromatin and the binding of activating and inhibitory proteins to promoter and enhancer elements. Post-transcriptional control is mediated through mRNA localization and mRNA stability while post-translational control occurs through the activation of protein kinase R by the 5′ portion of the mRNA, protein folding within the endoplasmic reticulum and the possible interaction of the mRNA with microRNAs. The biological effects of IFN-γ are widespread, as almost every cell type is altered upon interaction with this protein. Thus it has become very apparent that IFN-γ is a multipotent cytokine whose regulation and effects are complex and essential to host survival.