Reversible epidermal growth factor receptor tyrosine kinase inhibitors are often used for the treatment of non-small cell lung cancer following failure of cytotoxic chemotherapy. While these agents are active in a subset of patients, most develop resistance and progress within the course of 1 year. In nearly half of the cases, acquired resistance is caused by a secondary epidermal growth factor receptor T790M mutation. Irreversible epidermal growth factor receptor tyrosine kinase inhibitors are an emerging class of agents that may have the potential to overcome and prevent the emergence of such mutation-related resistance.