Afatinib is an oral, irreversible ErbB family blocker indicated for first-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients with non-resistant epidermal growth factor receptor (EGFR) mutations. Afatinib is also approved for the treatment of metastatic squamous NSCLC following progression on platinum-based chemotherapy. Common afatinib-associated toxicities include gastrointestinal and dermatologic events, which can be dose limiting.In this review, the authors describe clinical trial experiences with afatinib, as well as best practices and practical approaches to the management of afatinib-associated adverse events in EGFR mutation-positive NSCLC.Safety and tolerability data from phase 3 trials of afatinib were reviewed, together with real-life experiences from the authors' clinical practices.Patient education, combined with early assessment and effective management of afatinib-related adverse events as well as dose- reduction strategies, allows patients to continue treatment and maximize the clinical benefits of afatinib.