The aim of this study was to investigate the in vitro fatigue behavior of a dental bonding system [ScotchBond Multi Purpose (SBMP)] by using a cyclic shear loading test. Cylinders of a light-cured hybrid composite resin (Z100) were formed on, and bonded with SBMP to, the flattened, acid-etched enamel surface of human teeth. Thirty-two samples (eight per group) were used to determine the 1-h, 1-day, 7-day, and 30-day shear bond strengths. For the shear fatigue test, the stress was cycled, at a rate of 1 Hz, between 0 and a present value in the 12-28 MPa range (from -3 SD to +1 SD around the 24-MPa mean bond strength of the 1-h specimens). The applied stress and the number of cycles to failure were recorded for each of the 75 samples tested (15 samples per set-stress). Three stress versus number of cycles curves (low, median, and high S-N curves) were obtained and an approximate endurance limit of 10 MPa was identified for the SBMP bonding system. The data obtained explain, in part, the discrepancy between in vitro and in vivo results and underline the difficulty of predicting the in vivo behavior based on results of in vitro bond strength tests alone. Shear fatigue test data, however, could provide a better insight into the long-term in vivo behavior of a dental bonding system.