A new generation of biomarkers has become available with the discovery of the genetic alterations such as single-base substitutions, insertions, deletions, and translocations that are responsible for the development and progression of virtually all human cancers. However, it is often difficult in clinical practice to obtain sufficient tumor material for genetic analyses. Some tumors such as advanced non-small cell lung cancer are only accessible through biopsies with frequently insufficient tumor material available for genotyping. Moreover, in many patients with advanced or progressing disease it can be challenging or even impossible to acquire tumor tissue samples. In addition, in patients treated with molecular targeted therapy, clinicians frequently search for early evidence of recurrence or mechanisms underlying resistance. In these cases, the analyses of tumor-specific genetic alterations in the serum or plasma of the patients are particularly valuable because they can provide temporal measurements of the total tumor burden as well as identify specific mutations that arise during therapy. Blood samples are more easily and frequently accessible and are therefore employed to detect tumor-specific genetic alterations. This procedure is termed “liquid biopsy”.