This paper considers the use of on-line structural health monitoring in advanced nuclear power systems such as IRIS. The motivation for the on-line health monitoring is to prevent routine maintenance from interrupting long-term continuous reactor operation. However, the outcome of the on-line monitoring implementation has a broader impact, and amounts to a paradigm shift in maintenance strategy from outage-based maintenance to continuous real-time monitoring of operational and structural integrity. Indeed, on-line health monitoring data will provide a foundation for diagnostics and prognostics (i.e., predictive) capabilities that will detect component degradation prior to failure, thus allowing for proactive rather than reactive maintenance strategies. Specifically, this paper briefly reports on our studies on (1) on-line monitoring strategy and its benefits, (2) candidate reactor components where on-line monitoring provides maximum benefits, (3) applicable on-line NDE sensor methodologies and conceptual sensor designs, and (4) model-based sensor performance estimations.