β-Lactamases can be named on the basis of molecular characteristics or functional properties. Molecular classes A, B, C, and D define an enzyme according to amino acid sequence and conserved motifs. Functional groups 1, 2, and 3 are used to assign a clinically useful description to a family of enzymes, with subgroups designated according to substrate and inhibitor profiles. In addition, other designations are used to define the functionality of specific subgroups, such as extended-spectrum β-lactamases, or ESBLs, and inhibitor-resistant TEM, or IRT, β-lactamases. None of these systems provides an unambiguous description of this versatile set of enzymes. A proposed classification system involving microbiological, molecular, and biochemical properties is described, based on the traditional classes A, B, C, and D and functional groups 1, 2, and 3 designations.