Circulating free DNA (cfDNA) is genetic material released from various cells into bodily fluids. Among its fractions, circulating tumor DNA (ctDNA) originates from tumor cells and reflects their genetic material, including mutations and epigenetic changes. Methods commonly employed for detecting ctDNA in blood include next-generation sequencing (NGS) and various types of PCR. The presence of ctDNA can be utilized in liquid biopsies for many diagnostic purposes related to various cancers. It is a minimally invasive method of sampling molecular compounds from tumor cells. In this paper, we focus on current knowledge regarding the liquid biopsy of blood ctDNA in the context of lung cancer, one of the leading causes of cancer-related mortality. Currently, as a clinically approved method, liquid biopsy serves as a complementary technique in NSCLC diagnostic and genetic profiling. Other applications of liquid biopsy that are still being investigated include the detection of minimal residual disease (MRD) after curative treatment and response monitoring to systemic treatment. This review discusses current and future potential directions for the development and implementation of ctDNA for patients with NSCLC.