In this review, we were able to identify EPHA2, EPHA3, EPHA5, EPHA7, EPHB4, EPHB6, ephrin-A1, ephrin-A2, ephrin-B2, and ephrin-B3 as potential targets of novel therapeutic agents, alone or in combination with well-established therapies (Figure 1 and Figure 2), and to demonstrate that their pharmaceutical up- or downregulation may lead to profound (N)SCLC suppression both in vitro and in vivo. Here, EPHB4 is linked to small cell lung carcinoma.