We discuss the development of a comprehensive remote patient monitoring system that facilitates the self-care of patients undergoing nocturnal home hemodialysis (NHHD), a complex hospital-at-home therapy. The use of a continuous, iterative approach with user involvement for the validation of assumptions can avoid situations where the system serves a patient poorly. An ethnographic analysis was used to determine specific design principles, which were reviewed with the patients prior to development of the system. Iterative designs were tested through usability testing and further validation was done with a member-checking exercise. Patients expressed concern about the physical obtrusiveness of monitoring which, consequently, led to a lack of adherence. The need for monitoring the integrity of the bloodlines was identified as important because one of the most significant fears among patients was potential blood loss. Patients expressed a need for immediate human intervention in response to an alert. The use of ethnography, usability testing, and member-checking methods in a user-centered approach to design can result in systems that better meet the needs of the patients and caregivers alike.