Monoclonal antibodies targeting the PD-1/PD-L1 immune checkpoint have emerged as efficient cancer biotherapeutics. In parallel, small molecules targeting PD-L1 are actively searched to offer novel therapeutic opportunities and to reduce treatment costs. Thus far, all PD-L1 small molecule inhibitors identified present the unique property to induce and to stabilize the formation of PD-L1 protein homodimers. PD-L1 itself can form heterodimers with B7-1 (CD80) but it is essentially monomeric in solution, although the homolog viral protein vOX2 is known to dimerize. Drug-induced sequestration of PD-L1 homodimers prevents binding of PD-L1 to PD-1, thus blocking the downstream signaling. We have analyzed this phenomenon of drug-induced protein dimerization to show that PD-L1 is not an isolated case. Several examples of drug-mediated protein homodimer stabilization are presented here. In particular, a similar phenomenon has been observed with small molecules, such as NSC13728 and KI-MS2-008, which stabilize Max-Max protein homodimers, to block the formation of Myc-Max heterodimers and the ensuing signalization. PD-L1, Max and ten other examples of drug-stabilized protein homodimers point to a general mechanism of protein regulation by small molecules. Nevertheless, the extent and functions of drug-induced PD-L1 homodimers await validation in vivo.