Molecular and cellular effects of lifelong or even multigenerational exposure of phytoestrogens (PEs) are still controversially discussed and gain substantial public attention. While PE-rich diets may be preventive towards menopausal complications as well towards hormone dependent cancer formation, it seems as if late PE exposure at an advanced age results in increased risk of hormonal carcinogenesis in certain animal studies. Long-term epidemiological studies imply a protective effect of PEs on breast tissue as indicated by reduced rates of breast cancer in countries with high consumption of PE-rich soy products, as in Southeast Asia. Although, it is still speculative if the biological effects of soy products derive only from the contained PE. It is known for a number of endocrine modulating substances that the timing of exposure is a crucial element of its final effects. Therefore, exposure during critical developmental windows, such as the embryonal or fetal, the early postnatal and pubertal period, is most likely to have an important impact and result in longest-lasting effects. Thus, these effects may not only result from direct exposure to specific tissues but also by germline modifications. In summary, a number of new studies demonstrate that lifelong PE exposure is able to affect estrogen sensitive tissues, apparently in a tissue selective manner, effects which differ from later life exposure. With respect to health risks and benefits, these data indicates that the situation is much more complex then expected, and these results are highly relevant for the interpretation of regional differences in endocrine-related cancer incidence.