The human epidermal growth factor receptor family is composed of four tyrosine kinase receptors (HER-1 or EGFR, HER-2, HER-3 and HER-4). Human epidermal growth factor receptor pathways play a critical role in human cancer and are involved in tumour proliferation, apoptosis, angiogenesis, and cell migration/invasion. Pan-HER inhibitors such as afatinib, dacomitinib, and neratinib induce irreversible inhibition of all the dimers formed by the human epidermal growth factor receptor family. In clinical practice, only afatinib is approved by the Food and Drug Administration for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumours have epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations. Today, those molecules are still in development and their activity and safety investigated in clinical trials. The most common adverse effects of the pan-HER inhibitors are diarrhoea and skin toxicity.