Sex biases in autoimmunity and infection, together with immune cell expression of estrogen and androgen receptors, suggest that sex steroid hormones directly modulate immune cells, although the mechanism(s) by which this might occur is not completely understood. The female predisposition to autoimmunity, and alteration of disease symptoms during pregnancy, has led to the idea that lower physiological amounts of estrogen are stimulatory to the immune system, while pharmacological doses or pregnancy levels of estrogen modulate cell mediated immunity. These differences in immune function during naturally occurring variation in estrogen levels have been corroborated through studies of exogenous estrogen treatment in vivo or in vitro. The resolution of immune responses is dependent upon the nature of soluble mediators produced by the innate and adaptive immune system, and estrogen modulation of cytokine and chemokine profiles often correlates with amelioration or exacerbation of autoimmunity. In this review, we will summarize recently published studies that demonstrate effects of estrogen on autoimmune responses in humans and in murine model systems, with a focus on CD4+ T helper cell differentiation and cytokine production, B cell function and autoantibody production, hematopoietic cell differentiation and proinflammatory estrogen metabolites. It is of interest to understand the effects of estrogens on both normal immunity and autoimmune disease models because both estrogens and selective estrogen receptor modulators currently are being assessed for clinical efficacy in the treatment of autoimmunity and cancer.