The prevalence of diabetes is lower in premenopausal women, especially diabetic syndromes with insulin deficiency, suggesting that the female hormone 17β-estradiol protects pancreatic β-cell function. In classical rodent models of β-cell failure, 17β-estradiol at physiological concentrations protects pancreatic β-cells against lipotoxicity, oxidative stress, and apoptosis. In this review, we integrate evidence showing that estrogens and their receptors have direct effects on islet biology. The estrogen receptor (ER)-α, ERβ, and the G-protein coupled ER are present in β-cells and enhance islet survival. They also improve islet lipid homeostasis and insulin biosynthesis. We also discuss evidence that ERs modulate insulin sensitivity and energy homeostasis, which indirectly alter β-cell biology in diabetic and obese conditions.