During evening rush hour traffic on August 1, 2007, the major interstate highway bridge carrying I35W over the Mississippi River in Minneapolis catastrophically failed, tragically taking the lives of thirteen people and injuring many more. The steel truss bridge, constructed in 1967, was undergoing deck reconstruction during the collapse, and was estimated to carry more than 140,000 vehicles daily. This tragedy generated great interest in employment of structural health monitoring systems. The I35W St. Anthony Falls Bridge, a post-tensioned concrete box bridge constructed to replace the collapsed steel truss bridge, contains over 500 instruments to monitor the structural behavior. Numerical models of the bridge are being developed and calibrated to the collected data obtained from truck load tests and thermal effects. The data obtained over the first few years of monitoring are being correlated with the calibrated models and used to develop the baseline bridge behavior. This information is being used to develop a system to monitor and interpret the long-term behavior of the bridge. This paper describes the instrumentation, preliminary results from the data and model calibration, the plan for developing long-term monitoring capabilities, and the challenges associated with structural health monitoring of bridge systems. In addition, opportunities and directions for future research required to fully realize the objectives of structural health monitoring are described.