The shape of the genome is thought to play an important part in the coordination of transcription and other DNA-metabolic processes. Chromosome conformation capture (3C) technology allows us to analyze the folding of chromatin in the native cellular state at a resolution beyond that provided by current microscopy techniques. It has been used, for example, to demonstrate that regulatory DNA elements communicate with distant target genes through direct physical interactions that loop out the intervening chromatin fiber. Here we discuss the intricacies of 3C and new 3C-based methods including the 4C, 5C and ChIP-loop assay.