The effect of various pretreatments on the bonding of a resin cement to resin-composite CAD/CAM blocks (RCBs) was examined. The surface of dispersed-filler RCBs (DF-RCBs) and a polymer infiltrated ceramic network RCB (PICN-RCB) was roughened using hydrofluoric acid etching (HF) or sandblasting, and followed by silanization and/or universal adhesive (UA) application. Microtensile bond strength (µTBS), surface roughness parameters (arithmetical mean height (Sa); developed interfacial area ratio (Sdr)), and critical surface energy (γc) were determined. For most DF-RCBs, the highest µTBS was obtained using HF+UA. UA application to DF-RCBs resulted in similar or higher µTBS compared to silanization, which indicates that silane treatment is not crucial for DF-RCBs, especially after HF. In contrast, the highest µTBS to PICN-RCB was obtained with silanization. Both roughening pretreatments significantly increased the surface roughness parameters and the γc of all RCBs. The γc was positively correlated with Sa (r=0.756, p<0.001) and Sdr (r=0.837, p<0.001).