Bacterial strains belonging to the same species vary considerably in gene content. Thus, the genetic repertoire of a given species (its "pan-genome") is much larger than the gene content of individual strains. These variations in DNA material, together with differences in genomic structure and nucleotide polymorphisms among strains, confer upon prokaryotic species a phenomenal adaptability. Although the approach of sequencing multiple strains from a single species remains the main and often easiest way to study the pan-genome, feasible alternatives include those related to DNA hybridization. In other cases, the use of metagenomic sequences is already applicable by data mining from the growing metagenomic databases. Eventually, the single-cell genome approach might be the ideal solution. The pan-genome concept has important consequences for the way we understand bacterial evolution, adaptation, and population structure, as well as for more applied issues such as vaccine design or the identification of virulence genes.