The third-generation Honda CR-V (RE1–RE7) launched in late 2006. It abandoned the exterior side-hinged tailgate with a mounted spare wheel in favor of a traditional top-hinged rear hatch and under-floor spare placement. Lowered overall vehicle height and center of gravity brought car-like handling characteristics and highway stability.

Engines included a 2.0-liter R20A i-VTEC (150 hp), a 2.4-liter K24Z (166–170 hp), and 2.2-liter i-CTDi / i-DTEC turbodiesels (140–150 hp). Advanced optional technology debuted, including Collision Mitigation Braking System (CMBS) and Adaptive Cruise Control. A 2009 refresh brought subtle bumper sculpting, a revised front grille, and enhanced noise vibration dampening.