Purpose: To investigate the effects of different combinations of self-adhesive resin cements and surface treatments on the microtensile bond strength (μTBS) of different CAD/CAM resin-matrix ceramics. Materials and Methods: Two different types of CAD/CAM resin-matrix ceramics (LAVA Ultimate [LU] and Vita Enamic [VE]) were used. Slices 5 mm in thickness were obtained from each CAD/CAM material. Samples of each ceramic were randomly separated into the following surface treatment groups: (1) Control group with no surface treatment; (2) 9.5% hydrofluoric acid (HF) + universal adhesive (UA, Single Bond Universal, 3M ESPE); and (3) Sandblasting with 50-μm aluminum oxide particles (SN) + UA. Two different types of recently developed resin cement (RelyX U200, 3M ESPE; SET PP, SDI Dental Limited) were applied to the treated ceramic slices in each group. After 24 hours, parallel sections were removed from the specimens, and microbeam-shaped sticks (1.0 × 1.0 × 10 mm) were prepared. The μTBS test was performed, and the data were statistically analyzed. Results: Statistical analyses revealed differences among the study groups (P .05). The control groups of each resin cement exhibited lower μTBS values than the groups that received surface treatment (P .05). The effect of surface treatment on μTBS (partial eta-squared [ηp2] = 0.381) was more significant than the effects of ceramic (ηp2 = 0.267) and self-adhesive resin cement (ηp2 = 0.184). Conclusion: Surface treatment is the most important factor affecting the μTBS of resin cement to CAD/CAM materials, followed by the type of resin-matrix ceramic and the type of resin cement, respectively.