Bag-1 is an anti-apoptotic protein that exhibits altered expression in many malignancies, including oral squamous cell carcinoma. The bag-1 gene gives rise to different protein products with different subcellular localisations through alternative translational initiation sites. In oral squamous cell carcinoma, cytoplasmic expression has been associated with metastasis to regional lymph nodes and poor prognosis. In contrast, the longest Bag-1 isoform is nuclear and may regulate differentiation in oral epithelium. In this review, the functions of the three isoforms of Bag-1 expressed in oral epithelial cells are discussed in relation to their contribution to oral carcinogenesis.