We present a new classification scheme for amino acids and nucleobases based on the electronic properties of the individual molecules. Using chemical reactivity indices such as electronegativity, electrophilicity, and chemical hardness, we can identify similarities and differences between each class of amino acids and nucleobases. Notable differences emerge in particular with regard to high, neutral or low electronegativity as well as different combinations of chemical hardness. Our approach allows us to relate these insights to the properties of the side groups in terms of a unique reference scheme. We further show that hydrophobic differences between amino acids are rather negligible in the context of electronic properties. Our classification scheme also rationalizes the occurrence of distinct stable nucleobase pairs and clearly emphasizes certain differences between individual molecules. The stability and abundant occurrence of Watson–Crick nucleobase pairs is further discussed in the context of the minimum electrophilicity principle.