The effects of estrogen in breast epithelial cells are mediated primarily via estrogen receptor alpha and estrogen receptor beta (ERalpha and ERbeta). Accumulating evidence implicates a role for Ca2+ and calmodulin in breast carcinoma, as well as in the function of ERalpha. Calmodulin contributes to the regulation of both ERalpha degradation and ERalpha-mediated transcriptional activation. Recent data will be summarized in this review. Models to explain the molecular mechanisms by which calmodulin modulates ERalpha function are proposed.