Neurons in the hypothalamus play central roles in physiology and behavior, and their loss or dysfunction cause common human diseases such as obesity and the sleep disorder narcolepsy. Efforts to study these diseases have been hindered by the inaccessibility of human hypothalamic neurons. I developed a robust method to generate hypothalamic neurons from human embryonic and induced pluripotent stem cells. These stem cell-derived hypothalamic neurons include the AGRP and POMC neurons that regulate feeding and the hypocretin/orexin neurons that regulate sleep and are lost in narcolepsy. Stem cell-derived neurons express the expected marker genes, have the characteristic morphology of their in vivo counterparts, and survive transplantation into the mouse brain. Using the CRISPR/Cas9 system I have generated knock-in reporters for multiple hypothalamic neuron types and introduced disease-associated genetic variants. I will use these cellular models to study the phenotypic consequences of common and rare genetic variants in disease-relevant cell types.