The ultimate goal of this Tools and Technology Grant was to develop methods to differentiate human induced pluripotent stem cells (iPSCs) into microglia, the principle immune cell of the brain. Microglia have implicated in virtually every neurological disorder including Alzheimer’s Disease, traumatic brain injury, and stroke and yet studies of human microglia have been greatly limited because of the considerable difficulty of obtaining and growing these cells. By developing methods to coax human iPSCs into becoming microglia, we aimed to provide a renewable and expendable source of these important cells that researchers worldwide could use to study an array of human neurological diseases and injuries. We are delighted to report that our team was successful in this endeavor and established a fully-defined and highly reproducible method to differentiate iPSCs into microglia (Abud et. al., Neuron, 2017). From 1 million starting iPSCs we are able to generate well over 50 million microglia. By closely examining micoglial gene expression and function, we have also confirmed that the resulting microglia are extremely similar to human brain-derived microglia. Importantly, many independent labs have now replicated our approach and are using these methods to perform cutting edge research on a variety of human diseases ranging from Alzheimer’s and Parkinson’s Disease to Autism, Schizophrenia, and traumatic brain injury. To test the utility of this new model to study Alzheimer’s Disease we have used siRNA and CRISPR gene editing technology to manipulate the expression of two genes that are implicated in the development of Alzheimer’s Disease and highly expressed in human microglia. Our findings have revealed important new functions for these genes and are helping to clarify how these mutations effect disease risk.