Liquid biopsy is a promising tool in oncology that offers a minimally invasive alternative to traditional tissue biopsies. It involves the analysis of circulating nucleic acids, such as cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA), as well as circulating tumor cells (CTCs), typically from blood. Liquid biopsies have diverse clinical applications, including cancer screening, early detection, initial diagnosis, cancer genotyping, prognostication, monitoring of treatment response and resistance, and detection of resistance mechanisms. They also aid in the differentiation of immune checkpoint blockade response patterns and the personalization of adjuvant or additive therapy via minimal residual disease (MRD) monitoring. Liquid biopsies provide real-time molecular insights, can be collected serially, and offer a more holistic evaluation of a patient's disease by assessing material from all tumor sites. They are less invasive and have quicker turnaround times compared to tissue biopsies. However, challenges remain, such as detecting low amounts of tumor deposits in peripheral blood and potential false positives from clonal hematopoietic mutations. The clinical utility of liquid biopsies needs further validation, and ongoing research, including trials using alternate bodily fluids and AI technology, is expected to enhance their application. In early-stage cancer, liquid biopsies are used for prognostication, personalization of adjuvant therapy, and molecular relapse monitoring. ctDNA positivity after curative therapy is associated with higher risk of recurrence and can guide treatment decisions. In advanced cancer, liquid biopsies are used for evaluating targetable alterations, prognostication, and assessing response to checkpoint inhibitor (CPI) therapy. They also help in detecting resistance mechanisms and monitoring treatment response to targeted therapy and chemotherapy. FDA-approved liquid biopsy companion diagnostics, such as those for EGFR and PIK3CA alterations, are already available. Future perspectives include the integration of AI in liquid biopsy analytics and the expansion of liquid biopsy applications to alternative bodily fluids. Despite challenges, liquid biopsies are expected to play a significant role in precision oncology, improving patient outcomes through better treatment decisions and personalized care.Liquid biopsy is a promising tool in oncology that offers a minimally invasive alternative to traditional tissue biopsies. It involves the analysis of circulating nucleic acids, such as cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA), as well as circulating tumor cells (CTCs), typically from blood. Liquid biopsies have diverse clinical applications, including cancer screening, early detection, initial diagnosis, cancer genotyping, prognostication, monitoring of treatment response and resistance, and detection of resistance mechanisms. They also aid in the differentiation of immune checkpoint blockade response patterns and the personalization of adjuvant or additive therapy via minimal residual disease (MRD) monitoring. Liquid biopsies provide real-time molecular insights, can be collected serially, and offer a more holistic evaluation of a patient's disease by assessing material from all tumor sites. They are less invasive and have quicker turnaround times compared to tissue biopsies. However, challenges remain, such as detecting low amounts of tumor deposits in peripheral blood and potential false positives from clonal hematopoietic mutations. The clinical utility of liquid biopsies needs further validation, and ongoing research, including trials using alternate bodily fluids and AI technology, is expected to enhance their application. In early-stage cancer, liquid biopsies are used for prognostication, personalization of adjuvant therapy, and molecular relapse monitoring. ctDNA positivity after curative therapy is associated with higher risk of recurrence and can guide treatment decisions. In advanced cancer, liquid biopsies are used for evaluating targetable alterations, prognostication, and assessing response to checkpoint inhibitor (CPI) therapy. They also help in detecting resistance mechanisms and monitoring treatment response to targeted therapy and chemotherapy. FDA-approved liquid biopsy companion diagnostics, such as those for EGFR and PIK3CA alterations, are already available. Future perspectives include the integration of AI in liquid biopsy analytics and the expansion of liquid biopsy applications to alternative bodily fluids. Despite challenges, liquid biopsies are expected to play a significant role in precision oncology, improving patient outcomes through better treatment decisions and personalized care.