The set of interaction energies for 22 systems of biological importance, developed by Jurečka et al. [Phys. Chem. Chem. Phys., 2006, 8, 1985] and called S22, became an often used benchmark for evaluating the performance of various computational methods. As the quality of such methods improves, the uncertainties of the S22 energies are becoming too large to enable meaningful comparisons. We therefore improved the benchmarks by performing calculations in larger basis sets than used by Jurečka et al. The basis extensions included additions of higher angular momentum, diffuse, and midbond functions. The percentage deviations of the original S22 interaction energies from our values are up to 15.4%. We have estimated that the average (unsigned) uncertainty of our results should be about 1.0%. This estimate includes contributions from basis set truncation, frozen-core approximation, and neglected electron excitations.