The transcription factor activator protein-1 (AP-1) has been implicated as a driver of carcinogenesis since its original characterization. Oncogenic transcription factors like AP-1 are becoming new targets for cancer intervention. Inhibitors of AP-1 have been shown to block tumor promotion, transformation, progression and invasion. The Fos related antigen-1 (Fra-1) is activated in multiple cancers and gene ablation can suppress the invasive phenotypes of many tumor cell lines. This review focuses on the regulation of fosl1 expression, stabilization and activation of the Fra-1 polypeptide and on Fra-1-mediated tumorigenesis.