The starting point of this paper is the analysis of the reference problem in intra-cerebral electroencephalographic (iEEG) recordings. It is well accepted that both surface and depth EEG signals are always recorded with respect to some unknown time-varying signal called reference. This article discusses different methods for determining and reducing the influence of the reference signal for the iEEG signals. In particular, we derive optimal approaches for the estimation of the reference signal in iEEG recording setups and demonstrate their relation to the well known Minimum Power/Variance Distortionless Response (MPDR/MVDR) approaches derived for general array and antenna signal processing applications. We show that the proposed approaches achieve optimal performance in terms of estimation error and that they outperform other reference identification methods proposed in the literature. The developed algorithms are illustrated on simulated examples and on real iEEG signals.