The penicillin-binding proteins (PBPs) are the target enzyme family of the β-lactams. From the evolutionary point of view, PBPs and β-lactamases are related to each other with PBPs being the ancestors. Inhibitors of the β-lactamases are capable of restoring the activity of the β-lactam antibiotics in resistant strains. The comparison with the PBPs shows that the β-lactamases are no longer able to harbor a peptidoglycan. In turn, β-lactamases have learnt to deal with different β-lactam antibiotics. The carbapenems, being a substrate for the class D lactamase, consist of 6-hydroxyethyl side chain, which plays an important role in the degradation of the β-lactam ring. The parentally administered broad-spectrum carbapenems are especially active against Gram-positive and -negative aerobic and anaerobic bacteria and are stable against serine-β-lactamases. In β-lactamases, a basic amino acid, such as lysine or glutamine, activates the serine-OH by taking over the proton.