Histone variants are proteins that substitute for the core canonical histones (H3, H4, H2A, H2B) in nucleosomes in eukaryotes and often confer specific structural and functional features. The term might also include a set of linker histone (H1) variants, which lack a distinct canonical isoform. The differences between the core canonical histones and their variants can be summarized as follows: (1) canonical histones are replication-dependent and are expressed during the S-phase of cell cycle whereas histone variants are replication-independent and are expressed during the whole cell cycle; (2) in animals, the genes encoding canonical histones are typically clustered along the chromosome, are present in multiple copies and are among the most conserved proteins known, whereas histone variants are often single-copy genes and show high degree of variation among species; (3) canonical histone genes lack introns and use a stem loop structure at the 3’ end of their mRNA, whereas histone variant genes may have introns and their mRNA tail is usually polyadenylated. Complex multicellular organisms typically have a large number of histone variants providing a variety of different functions. Recent data are accumulating about the roles of diverse histone variants highlighting the functional links between variants and the delicate regulation of organism development.