This paper presents a cylinder pressure-based control (CPBC) system for conventional diesel combustion with high EGR levels. Besides the commonly applied heat release estimation, the CPBC system is extended with a new virtual NOx and PM sensor. Using available cylinder pressure information, these emissions are estimated using a physically based combustion model. This opens the route to advanced On-Board Diagnostics and to optimized fuel consumption and emissions during all operating conditions.The potential of closed-loop CA50 and IMEP control is demonstrated on a multi-cylinder heavy-duty EGR engine. For uncalibrated injectors and fuel variations, the combustion control system makes the engine performance robust for the applied variations and reduces the need for a time-consuming calibration process. Cylinder balancing is shown to enable auto-calibration of fuel injectors and to enhance fuel flexibility. For both Biodiesel and US diesel, the effects on NOx and PM emissions are partly compensated for by combined CA50 and IMEP control. This can be further improved by application of (virtual) emission sensors. Furthermore, it is shown that this combustion controller shows good transient performance during load changes.The virtual emission sensor is successfully implemented for real-time control. For operating conditions with high EGR rates and varying injection timing, the predictions of the virtual NOx and PM sensor are compared with measurements. NOx emission prediction inaccuracy is typically on the order of 12%, which is comparable to commercially available sensors. The predicted PM emissions show good qualitative agreement, but need further improvement for application in DPF regeneration and PM emission control strategies. Robust emission control is essential to meet future requirements for On-Board Diagnostics and In-Use Compliance.