Purpose: To evaluate the microshear bond strength (μSBS) of several universal adhesive systems applied on five different indirect restorative materials. Materials and Methods: Five CAD/CAM materials were selected: 1) indirect resin composite (LAV); 2) feldspathic glass ceramic (VTR); 3) leucite-reinforced glass-ceramic (EMP); 4) lithium disilicate ceramic (EMX); 5) yttrium-stabilized zirconium dioxide (CZI). For each material, 15 blocks were cut into 4 rectangular sections (6 × 6 × 6 mm) (n = 60 per group), and processed as recommended by the respective manufacturer. For each indirect material, the following adhesive systems were applied according to the respective manufacturer's instructions: 1) AdheSE Universal [ADU]; 2) All-Bond Universal (ABU); 3) Ambar Universal (AMB); 4) Clearfil Universal (CFU); 5) Futurabond U (FBU); 6) One Coat 7 Universal (OCU); 7) Peak Universal Bond (PUB); 8) Prime&Bond Elect (PBE); 9) Scotchbond Universal Adhesive (SBU); 10) Xeno Select (XEN, negative control). After the application of the adhesive system, cylinder-shaped transparent matrices were filled with a dual-curing resin cement (NX3) and light cured. Specimens were stored in water (37°C for 24 h) and tested in shear mode at 1.0 mm/min (mSBS). The failure pattern and μSBS were statistically evaluated (a = 0.05). Results: LAV, VTR, and EMP showed a greater number of cohesive fractures than EMX and CZI (p 0.0001). PUB was the only adhesive for which the mean μSBS reached the highest ranking of statistical significance for all five substrates. When each adhesive was compared across the five substrates, 8 out of 10 (ADU, ABU, AMB, CFU, OCU, PUB, PBE, and SBU) reached the statistically highest mean μSBS when applied on CZI. Conclusion: The specific chemical composition of universal adhesives was not the decisive factor in the bond strength values measured for different CAD/CAM indirect materials. There was a wide variability in mean μSBS when different universal adhesives were applied to the several CAD/CAM indirect materials. Most universal adhesives bonded well to air-abraded zirconia. Keywords: resin cement, universal dentin adhesive, CAD/CAM restorative materials, bond strength