The hypothalamus controls many homeostatic and instinctive physiological processes, including the sleep-wake cycle, food intake, and sexually dimorphic behaviors. These behaviors are regulated by environmental and physiological cues, although the molecular and cellular mechanisms that underlie these effects are still poorly understood. Recently, it has become clear that both the juvenile and adult hypothalamus exhibit neurogenesis, which modifies homeostatic neural circuitry. In this manuscript, we report data addressing the role of sex-specific and dietary factors in controlling neurogenesis in the mediobasal hypothalamus. We report that a high fat diet (HFD) activates neurogenesis in the median eminence (ME) of young adult female, but not male mice, and that focal irradiation of the ME in HFD-fed mice reduces weight gain in females, but not males. These results suggest that some physiological effects of HFD are mediated by sexually dimorphic neurogenesis in the ME. We present these findings in the context of other studies on the cellular and molecular mechanisms that regulate neurogenesis in postnatal and adult hypothalamus.