Automatic vibration-based structural health monitoring has been recognized as a useful alternative or addition to visual inspections or local non-destructive testing performed manually. It is, in particular, suitable for mechanical and aeronautical structures as well as on civil structures, including cultural heritage sites. The main challenge is to provide a robust damage diagnosis from the recorded vibration measurements, for which statistical signal processing methods are required. In this chapter, a damage detection method is presented that compares vibration measurements from the current system to a reference state in a hypothesis test, where datarelated uncertainties are taken into account. The computation of the test statistic on new measurements is straightforward and does not require a separate modal identification. The performance of the method is firstly shown on a steel frame structure in a laboratory experiment. Secondly, the application on real measurements on S101 Bridge is shown during a progressive damage test, where damage was successfully detected for different damage scenarios.