Non-small cell lung cancer is one of the leading causes of all cancer deaths, but despite years of research, it is still difficult to predict the response and clinical outcome of the disease. In recent years, new treatment strategies targeting the epidermal growth factor receptors (EGFR) have been developed. EGFR is one of the most frequently over expressed proteins in various cancers, including lung cancer, and signaling through this receptor has been known to cause tumor progression as well as resistance to different treatments. Therefore, EGFR has become an attractive target for various treatment strategies. However, it is important to note that not all patients with lung cancer are suitable for targeted treatment, and that patients should be selected for this treatment. Several studies have proven that the status of the EGFR can be both an indicator of suitability for treatment with, and predict the likelihood of response to EGFR targeted therapy. There are many standard techniques to be used for the detection of EGFR. This overview summarizes the ongoing and future investigations to determine the status of the EGFR.