Nuclear processes that silence plant transgenes are being revealed by analyses of natural triggers of epigenetic modifications, particularly cytosine methylation, and by comparisons of the genomic environments of differentially expressed transgene loci.  It is increasingly apparent that plant genomes can sense and respond to the presence of foreign DNA in certain sequence contexts and at multiple dispersed sites.  Determining the basis of this sensitivity and how nuclear defense systems are activated poses major challenges for the future.  This review focuses on silencing concerning positioning effects, which refer to repressive influences exerted on transgenes by flanking plant DNA and/or an unfavourable chromosomal location.  This type of silencing presumably reflects the epigenetic state of neighbouring host sequences or the relative tolerance of particular chromosome regions to invasion by alien DNA.  Often assumed in lieu of a better explanation, position effects are being clarified by analyses of the genomic environments of differentially expressed transgenes.  Further insight is coming from an improved understanding of the natural targets and signals for epigenetic modifications in eukaryotic genomes.