Abstract: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) comprise an effective therapy for advanced non-small cell lung cancer patients with EGFR-activating mutations. Unfortunately, most patients eventually develop resistance to EGFR-TKIs, probably due to a secondary point mutation of EGFR T790M. Thus, a sensitive method for accurate detection of T790M mutation is essential. Peripheral blood detection has gained our attention because it is convenient, making dynamic noninvasive quantitative detection of T790M mutation an optimal means of monitoring the efficacy of EGFR-TKIs. To date, the clinical significance of T790M mutation and EGFR-TKI resistance remains controversial. Several EGFR-TKIs targeting EGFR mutation, which have been introduced in recent years, showed better response in patients with T790M mutation, indicating that T790M may be a biomarker for conquering resistance. This review introduces the methodology of T790M detection and its role in clinical practice.