Mounting preclinical and clinical evidence indicate that indole-3-carbinol (I3C), a key bioactive food component in cruciferous vegetables, has multiple anticarcinogenic and antitumorigenic properties. Evidence that p21, p27, cyclin-dependent kinases, retinoblastoma, Bax/Bcl-2, cytochrome P-450 1A1 and GADD153 are targets for I3C already exists. Modification of nuclear transcription factors including Sp1, estrogen receptor, nuclear factor kappaB and aryl hydrocarbon receptor may represent a common site of action to help explain downstream cellular responses to dietary I3C and, ultimately, to its anticancer properties. While the current information is intriguing, future I3C research needs to focus on why these changes in nuclear transcription factors occur and how they relate to phenotypic responses and the quantity and duration of exposure to I3C and its dimer 3,3'-diindolylmethane.