To meet future emission targets, it becomes increasingly important to optimize the synergy between engine and aftertreatment system. By using an integrated control approach minimal fluid (fuel and DEF) consumption is targeted within the constraints of emission legislation during real-world operation. In such concept, the on-line availability of engine-out NOx emission is crucial. Here, the use of a Virtual NOx sensor is of great added value. Virtual sensing enables more direct and robust emission control allowing for example engine-out NOx determination during conditions in which the hardware sensor is not available. Furthermore, with use of the sensor, the engine control strategy can be directly based on NOx emission data, resulting in reduced response time and improved transient emission control. This paper presents the development and on-line implementation of a Virtual NOx sensor, using in-cylinder pressure as main input. The development steps from off-line modelling, calibration and validation towards real-time on-line implementation and validation will be presented in great detail. Here, focus is also on identifying the main sources for loss of absolute and relative NOx prediction accuracy when converting the off-line virtual sensor towards it’s on-line implementation. The Virtual NOx sensor is validated on a state-of-the-art EURO VI Heavy Duty Diesel Engine. Validation results demonstrate the application of the Virtual NOx sensor for improved transient emission control. Different control strategies using the Virtual NOx sensor as input will be addressed. As a next step and outlook, first results of the Virtual NOx sensor using the fueling strategy as main input, i.e. without the use of an in-cylinder pressure sensor, will also be discussed.