The cycle of patient- and genome-informed questions and answers in medicine. Set against familiar images depicting the water cycle, this analogy emphasizes the natural flow of such a process and the influence of environmental factors. The ground(work) of the genome medicine cycle is the front-line work directly with patients, families and populations. This feeds into the sea of questions to be addressed from clinical or research perspectives. Investigators work to illuminate the questions, and the research process raises information to a relatively amorphous position of potential impact. Information can be converted to knowledge and delivered through various conduits to patient care, which includes aspects of diagnosis, prediction and intervention, thereby maintaining the cycle.