Males and females have obvious phenotypic differences; they also exhibit differences related to health, life span, cognitive abilities and have different responses to diseases such as anemia, coronary heart disease, hypertension and renal dysfunction. Although the anatomical, hormonal and chemical differences between the sexes are well known, there are few molecular descriptors for gender-specific physiological traits and health risks. Recent studies using microarrays and other methods have made significant progress towards elucidating the molecular differences between mammalian sexes in a variety of tissues and towards identifying the transcription factors that regulate sex-biased gene expression. These findings are providing new insights into the molecular and genetic differences that dictate the different behaviors and physiologies of mammalian sexes.