Until recently the study of individual DNA sequences and of total DNA content (the C-value) sat at opposite ends of the spectrum in genome biology. For gene sequencers, the vast stretches of non-coding DNA found in eukaryotic genomes were largely considered to be an annoyance, whereas genome-size researchers attributed little relevance to specific nucleotide sequences. However, the dawn of comprehensive genome sequencing has allowed a new synergy between these fields, with sequence data providing novel insights into genome-size evolution, and with genome-size data being of both practical and theoretical significance for large-scale sequence analysis. In combination, these formerly disconnected disciplines are poised to deliver a greatly improved understanding of genome structure and evolution.