The major genetic factors affecting the expression of newly introduced genes in transgenic plants including epigenetic effects are summarized. Examples of (trans)gene silencing and the genetic signals involved are given. Based on current knowledge, several strategies to generate stable transgenic lines can be followed. Although initial laboratory and field tests over few generations allow good predictions about the long-term expression stability of single transgenic lines, the combination of different events by genetic crossing raises new questions. As different transgenic lines often carry the same or similar promoter elements and as coding regions may have sequence homologies, new epigenetic interactions can arise, thus justifying thorough expression testing of stacked transformation events obtained through cross-breeding.