Necessities and advantages of long-term health monitoring for a large bridge are briefly introduced, and practical plans of health monitoring (HM) for the Nanjing Yangtze River Bridge (NYRB) are proposed in this paper. The objective is to build a large HM system which consists of sensor system, signal sampling and processing system, and structural monitoring condition assessment system, and allows the bridge to be monitored and evaluated under normal operating conditions. Main monitoring items for the NYRB include environmental loads, structural responses and major diseases. By using MATLAB as a platform, programs will be developed to obtain useful information used to evaluate the safety and the remaining life of the NYRB. Combining theoretical analysis with measured vibration response data analysis, detailed plans including main monitoring items, layout of measuring points, transducers, amplifiers and methods of signal analysis and processing are determined and being implemented on the NYRB. Building this system will provide scientific basis for the bridge’s management and condition-based maintenance.