The conversion of CS2 with common carbonic anhydrase model systems has been studied using Hartree-Fock and density-functional theory methods employing the 6-311+G* basis set. The calculated geometries and energetical parameters for [L3ZnOH](+)/CS2 model systems (L = NH3, imidazole) are compared with those obtained previously for the CO2 hydration. While the same reaction mechanism applies for both heterocumulenes, the hypothetical conversion of CS2 to give [L3ZnSC(O)SH](+) is characterized by a higher barrier and is much more exothermic than the corresponding CO2 reaction cascade. Due to the increased number of heteroatoms, additional intermediates and product structures (compared with those involved in the CO2 conversion) must be taken into account and have been analyzed in detail. The smaller electrophilicity of CS2 is the reason for the higher activation energies, while the significantly increased exothermicity is due to the strong zinc(II)/sulfur interaction. The reversibility and therefore the existence of a catalytic cycle which could allow comparable CS2 transformations must be questioned. Nevertheless, an interesting field of stoichiometric zinc-mediated CS2 transformations is conceivable.