Amides are one of the most important functional groups in organic chemistry and play essential roles in both the pharmaceutical industry and life sciences. However, due to the natural reactivity of carboxylic acids and amines, their direct coupling is challenging and often leads to reactions that are not atom-economic and produce large amounts of nonrecoverable by-products. Despite the impressive number of coupling reagents available, sustainable methods for amide bond formation are still needed. To address this challenge, a new catalytic approach for the direct preparation of amides from carboxylic acids and amines is reported here. This method combines organocatalysis with a substoichiometric amount of activating agent under mild conditions (open air, room temperature, green solvents). This method was applied with good efficiency on a wide range of substrates, without epimerization of chiral stereocenters and on SPPS.