Natural killer (NK) cells are innate immune cells. Although NK cells are best characterized for their ability to control tumors and infections, recent data have indicated that they also are important regulatory cells by virtue of interactions with many types of immune and nonimmune cells. Thereby, they can affect the outcome of adaptive immune responses and maintain immune homeostasis. Thus, NK cells can either exacerbate or limit immune responses, including those to autoantigens. Here, we discuss current insights into the role of NK cells in human autoimmunity.