The electronic structure of the octahedral octasilasesquioxanes X8Si8O12(X = H, Cl or CH3) has been analysed in detail and the Si–X stretching mode investigated. It is amazing that among the many orbitals of H8Si8O12 there is exactly one of A2g symmetry. This pure oxygen lone-pair orbital turns out to be the highest occupied, followed by a number of oxygen lone pairs which interact very slightly with the Si and X atoms. The calculated first ionization energy of 10.7 eV is low but is in good agreement with experimental observations. Analysis of the reaction path of the few experimentally observed substitution reactions, Si–X + Y → Si–Y + X (X = H or Cl; Y = D, Cl, OCH3, or OSiMe3), on X8Si8O12, leads to the result that a five-co-ordinate silicon intermediate is involved, followed by concerted rearrangement of angles and bond distances. The reaction mechanism is dictated by the rigid structure of the Si8O12 framework. This does not allow pseudo-rotation or an attack from the back, thus leading to a new reaction path for four-co-ordinate silicon chemistry. Protonation of a bridging oxygen causes a small weakening of the Si–O bond only, in agreement with the stability of these molecules to acids. It is interesting that no adiabatic ground-state path exists to dissociate (HO)3Si–X into (HO)3Si + X for X = H, while one is expected to exist for X = Cl or CH3. Such a dissociative path is costly in energy in all cases, hence intermediates such as X7Si8O12 can be excluded for reactions of these molecules.