At present, Diesel engine combustion in most production engines is controlled via open-loop control. Increasing pressure from tightening emissions standards and on-board diagnosis requirements has made closed-loop combustion a possibility for production engines in the near future. For new combustion concepts, such as Homogeneous Charge Compression Ignition and other low NOx regimes, the need for closed-loop combustion control is very strong. In this work, the applicability of closed-loop combustion control for controlling the variability between cylinders in conventional Diesel combustion is explored through the use of a high-fidelity engine model. The problem is formulated such that the optimal performance of two different closed-loop control concepts can be evaluated through optimization rather than via control design. It is found that, for the types of disturbances occurring in a non-faulty engine, that control of individual cylinders leads to small performance gains compared to fuel bank control.