The M-Class was the first mainstream SUV from Mercedes-Benz. The second generation of the M-Class is a more road-oriented vehicle that reflects the trend for SUVs to adopt more car-like ride and handling. Competitors in this segment include the BMW X5, Infiniti FX, Cadillac SRX, and Volvo XC90. Mercedes-Benz offers several engine choices, ranging from a 3.5L V-6 to a 6.3 L V-8 (ML63 AMG), as well as a 3.2L V-6 diesel that is unique in its class. A standard 7-speed automatic is optimized for maximum fuel economy. All M-Class models feature standard 4WD, but without locking differentials. An optional off-road package adds a 2.93:1 low-range to the transmission for rock crawling adventures. Sport-oriented customers will prefer the ML63 AMG with its 503-bhp V-8, 20-inch alloy wheels, special AMG exterior trim, Nappa leather interior and bigger brakes. M-Class safety features for hilly terrain include DSR (Downhill Speed Regulation), Hill-Start Assist, and a special Off-Road Mode that changes the calibration of the powertrain and brake systems. Available features include 19-inch alloy wheels (N/A for ML63 AMG), adjustable height air suspension, Bi-Xenon headlights, DVD navigation, rear view camera, adaptive damping system, and walnut interior trim.

The ML450 HYBRID joins the lineup. The ML450 pairs a modified 3.5L V6 with electric motors. The ML450 can drive under electric power alone. The ML320 BlueTEC model is renamed ML350 BlueTEC.