Forty density functionals and one wavefunction method are assessed against a recently published database of accurate noncovalent interaction energies of biological importance. The comparison shows that two newly developed density functional theory (DFT) methods, PWB6K and M05-2X, give the best performance for this benchmark database of 22 noncovalent complexes, including both hydrogen-bonding and dispersion-dominated complexes. In contrast, the more popular B3LYP and PBEh functionals fail to describe the interactions in the dispersion-dominated complexes. The local spin density approximation and BHandH functionals give good performance for dispersion-dominated interactions at the expense of a large error for hydrogen bonding. PWB6K and M05-2X constitute a new generation of DFT methods based on simultaneously optimized exchange and correlation functionals that include kinetic energy density in both the exchange and correlation functional, and the present study confirms that they have greatly improved performance for noncovalent interactions as compared to previous DFT methods. We interpret this as being due to an improved treatment of medium-range correlation effects by the exchange-correlation functional. We recommend the PWB6K and M05-2X methods for investigating large biological systems and soft materials.