The nuclear factor of activated T cells (NFAT) family proteins are transcription factors that regulate the expression of a variety of target genes with or without forming complexes with other transcription factors. Although NFAT proteins have been extensively investigated and characterized in immune systems, their role in carcinogenesis are far from being understood. We, to our knowledge, are first to determine the potential involvement of the NFAT pathway in cell responses to carcinogen exposure. Experimental evidence accumulated from our studies indicate the critical role of NFAT3 in some carcinogen-induced cell transformation and tumorigenicity. Moreover, NFAT proteins have been found to be involved in cell cycle regulation, cell differentiation, cell survival, angiogenesis, and tumor cell invasion and metastasis. In the meantime, NFAT inhibitors are being developed with the ultimate aim to specifically switch off NFAT signaling without side effects. This review comprehensively reviews the results from the most recent studies, and also discusses some difficulties in current studies. To validate whether NFAT can be a promising target for chemoprevention, more research has to be done to further detail the roles of NFAT and to differentiate the functions of different members of this protein family in future studies.