Based on the evidence from epidemiological, animal, in vitro data and human clinical trials, it is evident that isoflavones are promising agents for breast cancer chemoprevention. It is also evident that the form of isoflavone used (purified vs soy products), dose of isoflavone used (low vs high), timing and duration of exposure of isoflavones appears to play a major role in determining agonistic or antagonistic effects. Collectively, these isoflavones have enough evidence to warrant use in a number of clinical trials to examine its efficacy as a potential chemopreventive agent for breast cancer. In this comprehensive review, we attempt to summarize the evidence demonstrating the potential use of isoflavones in breast cancer chemoprevention and the rationale to examine a combination of biochemical, morphological and molecular intermediate endpoint biomarkers of breast cancer risk to examine the efficacy of this promising agent.