There is growing recognition that the nervous and immune systems interact under both healthy and diseased conditions. This offers an excellent opportunity to define the role and molecular characteristics of neuroinflammation in neurodegenerative disorders. Chronic activation of the innate immune system is now well established as an underlying factor contributing to neurodegeneration—the progressive dysfunction and loss of neurons in the central nervous system leading to cognitive and motor disorders such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, and others. Microglia, the primary immune cells of the brain, are critical in the maintenance of brain homeostasis, but lose their functionality during the course of aging and neurodegenerative diseases. While the majority of innate immune responses to disease stressors are mediated by the microglia, perivascular macrophages and peripheral myeloid cell populations can also gain access to the diseased brain and participate in neuroinflammatory signaling. Thus, a better understanding of how immune responses regulate neuronal homeostasis, and of the circumstances leading to dysregulation in pathological conditions, is essential to developing effective therapies and mitigating disease impact. In this recorded webinar, speakers share their research on immune response–mediated onset of neurodegenerative diseases, and explain the genetic and physiological regulation of microglial function in both healthy and diseased states.