Two members of the quinoxaline antibiotic family, echinomycin and triostin A, form crystals complexed to a DNA fragment with the sequence d(CpGpTpApCpG). The crystal structure of both complexes was solved by X-ray diffraction to near-atomic resolution. The two structures are similar to each other with differences in some details due to the shorter cross bridge of echinomycin. Both molecules act as bis intercalators surrounding the d(CpG) sequence at either end of the double helix. Alanine forms sequence-specific hydrogen bonds to guanines in the minor groove. The two central AT base pairs are held together by Hoogsteen base pairing with adenine in the syn conformation in both complexes. An octahedrally hydrated magnesium ion is found in the crystal lattice that plays an important role in organizing the lattice as well as stabilizing the complex by hydrogen bonding both to base pairs of DNA and to the quinoxaline ring nitrogen atoms in the major groove side of the DNA double helix. A functional description of the various amino acids in quinoxaline antibiotics is given, together with possible modifications that might affect biological activity.