Liquid biopsy refers to a broad category of minimally invasive test done on blood or other fluid specimens to detect fragments of tumor-derived DNA, extracellular vesicles (EVs) and circulating tumor cells (CTCs). The most common method for liquid biopsy in lung cancer is the circulating tumor DNA (ctDNA), which may be used for the initial genotype profiling and detection of mechanisms of acquired resistance to targeted therapy. Other potential uses for ctDNA include evaluation of therapeutic response and detection of postsurgical minimal residual disease. In contrast to ctDNA which is originated from dying cells, EVs originates from living cells and may provide a better evaluation of the cancer biology. Early studies have shown comparable sensitivity for EVs and ctDNA in the detection of targetable alterations. CTCs may be useful to evaluate the risk of tumor relapse after treatment with curative intention.