Future progress in genetic research and technologies is likely to further increase the availability of interactive personal genomic information to non-experts. This trend raises technological, ethical, and regulatory concerns related to how people make sense of, engage with, and rely on their personal genomic data. Such concerns are not only of paramount importance for health professionals and policy makers, but are also a pressing issue for human-computer interaction (HCI) research. HCI tools, methods and practices can help make genomic information more accessible and understandable to non-experts. This authors make the argument that the complexity, importance, and personal relevance of this type of information makes understanding, informing, and empowering non-experts’ interaction with personal genomics a key challenge that lies ahead for the HCI community. This monograph explores the roles HCI can play in helping non-experts contribute, understand, engage with, and share their personal genomic information. It is also a call to action for those that are interested in the intersection of personal informatics and HCI, and, more broadly, in facilitating non-expert interaction with large amounts of complex, personal and uncertain information.