DNA replication and repair are critical processes that initiate, orchestrate, and affect a broad range of fundamental physiological reactions, ultimately promoting cell division, genome stability, and proper cellular physiology. Reflected in this, genes acting in DNA replication/repair and genome stability are required for disease suppression, and direct therapy responses. Their failure is correlated with genome instability, cancer, neurological defects, developmental delays, aging, metabolic disorders, inflammation and immune responses, and therapeutic drug reactions. Rooting in and extending from the rich history of deep mechanistic understanding of the field, this Keystone conference will highlight the latest advances and emerging concepts in the field, aspiring to prompt rich discussions in particular with its implications for medical biology, disease and treatment strategies.