Water is the ideal green solvent for organic reactions. However, most organic molecules are insoluble in it. Herein, we report a laboratory module that takes advantage of this property. The Passerini reaction, a three-component coupling involving an isocyanide, aldehyde, and carboxylic acid, typically requires [similar to] 24 h reaction times in organic solvents, but produces a quantitative conversion and yield in less than 30 min when performed in water. This rate enhancement allows the Passerini reaction to be easily adapted for use in a second-year organic laboratory course. Additionally, the incorporation of this laboratory module facilitates discussions of both green chemistry and combinatorial chemistry in the curriculum. (Contains 2 schemes and 2 notes.)