DNA topoisomerase II (topo II) is essential for survival of all eukaryotic cells. Topo II is both an enzyme and a structural component of the nuclear matrix. It regulates the topological states of DNA by transient cleavage, strand passing and re-ligation of double-stranded DNA resulting in decatenation of intertwined DNA molecules and relaxation of supercoiled DNA. Topo II plays an important role in DNA replication and is required for condensation and segregation of chromosomes. The expression of topo II is cell cycle dependent with both protein levels and catalytic activity peaking at G2/M. Phosphorylation/dephosphorylation of topo II may be a part of regulatory checkpoints at the entry and progression of mitosis.