In patients with non-small-cell lung cancer, the presence of brain metastases requires specific treatment due to the unfavourable overall impact of these lesions. Treatment with the tyrosine kinase inhibitor afatinib was shown to induce complete and long-lasting remissions in the five patients described here. All of them had multiple brain lesions and presented with symptoms. Study evidence suggests beneficial effects of afatinib in this respect, underlining these clinical observations. Afatinib might be incorporated into current treatment algorithms, allowing for the omission of radiotherapy, provided that larger phase III trials confirm the potential of epidermal growth factor receptor tyrosine kinase inhibitors in this respect.