The concept of a minimal cell is discussed from the viewpoint of comparative genomics. Analysis of published DNA content values determined for 641 different archaeal and bacterial species by pulsed field gel electrophoresis has lead to a more precise definition of the genome size ranges of free-living and host-associated organisms. DNA content is not an indicator of phylogenetic position. However, the smallest genomes in our sample do not have a random distribution in rRNA-based evolutionary trees, and are found mostly in (a) the basal branches of the tree where thermophiles are located; and (b) in late clades, such as those of Gram positive bacteria. While the smallest-known genome size for an endosymbiont is only 450 kb, no free-living prokaryote has been described to have genomes < 1450 kb. Estimates of the size of minimal gene complement can provide important insights in the primary biological functions required for a sustainable, reproducing cell nowadays and throughout evolutionary times, but definitions of the minimum cell is dependent on specific environments.