The chromosome conformation capture (3C) technique and its genome-wide applications (‘4C’) have identified a plethora of distal DNA sequences that are frequently in close spatial proximity. In many cases, these have been correlated with transcriptional regulation of the interacting genes, but the functional significance of many of the extreme long-range and interchromosomal interactions remains unclear. This review summarises our current understanding of how chromatin conformation can impinge on gene expression, the major questions that need to be addressed to understand this more fully, and how these questions may be answered in the near future.