Liquid biopsy has emerged not merely as a technological innovation, but as a new diagnostic paradigm driven by advances in sensitive molecular techniques, deeper understanding of cancer biology, and unmet clinical needs. Although tumor-derived materials in blood have been observed for decades, their clinical utilization has become feasible only in the last 10–20 years. Following FDA approval of ctDNA-based companion diagnostics, liquid biopsy began to be recognized as a core component of precision oncology rather than a supplemental tool. Its noninvasive nature allows repeated sampling, enabling longitudinal monitoring of tumors and capture of temporal and spatial heterogeneity. This fundamentally distinguishes liquid biopsy from tissue biopsy and imaging, which provide only static snapshots. Liquid biopsy is now being explored across the full clinical continuum, including early detection, treatment monitoring, MRD assessment, and resistance detection. At the same time, increasing regulatory engagement and industrial investment signal its transition from research to clinical practice. However, liquid biopsy does not yet fully replace tissue biopsy and requires careful biological interpretation. This chapter introduces the conceptual foundation and clinical rationale of liquid biopsy.