The interaction among biodiesel, engine calibration, and turbocharger system was investigated in a modern automotive diesel engine. In consideration of the poorer maximum torque curve derived from the use of fatty acid methyl ester (FAME) biodiesels, pure or in blends, with respect to the conventional diesel one, an experimental activity was dedicated to the investigation of the capability of the closed-loop combustion control (CLCC) technology to mitigate or improve the impact of FAME characteristics on the engine full torque curve. With respect to the well-known penalty effect of biodiesel on engine performance, the results highlighted the capability of the CLCC technology to reset the torque loss burning biodiesel. Furthermore, the study has provided evidence of the possibility to exploit the very low soot emissions burning FAME fuels, increasing the low-end maximum torque curve with respect to a conventional diesel fuel. The described engine re-optimization could be activated automatically in the engine electronic control unit, once a fuel-blending detection procedure based on the CLCC system (currently in development) has been implemented. In this respect, the study represents a further step toward the future actual full flex-fuel engine.