Many autoimmune rheumatic autoimmune disorders predominantly affect women. Sex hormones, in particular estrogen, can influence CD4 T-helper development and function. We highlight recent studies that begin to provide insights into the mechanisms by which estrogen modulates CD4 T-cell development and function, and thus potentially contribute to disease pathogenesis.High levels of estrogen can lead to thymic atrophy. Recent studies showed that this phenomenon results from effects of estrogen at multiple stages in early T-cell development. Estrogen is also known to affect mature CD4 T-cell function, and, in particular, their ability to produce selected cytokine profiles. The mechanisms by which estrogen can exert these effects were also recently explored and shown to include effects on expression of critical molecules known to be involved in these processes.Dissecting the molecular pathways employed by estrogen to modulate CD4 T cells will be critical in elucidating the manner by which estrogen exerts its effects on this compartment. Given that cell type specific differences underlie the ability of many hormonal therapies to exert tissue-specific estrogenic or antiestrogenic activities, this knowledge will be crucial to further exploitation of hormonal therapies in rheumatic autoimmune diseases.