In this work we test different strategies to compute high-level benchmark energies for medium-sized molecular clusters. We use the incremental scheme to obtain CCSD(T)/CBS energies for our test set and carefully validate the accuracy for binding energies by statistical measures. The local errors of the incremental scheme are <1kJ/mol. Since they are smaller than the basis set errors, we obtain higher total accuracy due to the applicability of larger basis sets. The final CCSD(T)/CBS benchmark values are ΔE=-278.01kJ/mol for (H2O)10,ΔE=-221.64kJ/mol for (HF)10,ΔE=-45.63kJ/mol for (CH4)10,ΔE=-19.52kJ/mol for (H2)20 and ΔE=-7.38kJ/mol for (H2)10.Furthermore we test state-of-the-art wave-function-based and DFT methods. Our benchmark data will be very useful for critical validations of new methods.We find focal-point-methods for estimating CCSD(T)/CBS energies to be highly accurate and efficient. For foQ-i3CCSD(T)—MP2/TZ we get a mean error of 0.34kJ/mol and a standard deviation of 0.39kJ/mol.