The paradigm that emerged from studies during the past decade established a central role for Jak–Stat (signal transducer and activator of transcription) signaling pathways in promoting the diverse cellular responses induced by interferon γ (IFN-γ). However, recent studies have shown that the IFN-γ receptor activates additional signaling pathways and can regulate gene expression by Stat1-independent pathways. The diversity of gene-expression patterns mediated by Stat1-dependent and -independent mechanisms and the balance between these two pathways play an important role in the biological response to IFN-γ.