Liquid biopsies, particularly circulating tumour DNA (ctDNA), are becoming increasingly important in cancer management. ctDNA is released into the bloodstream through cell death and may also be actively secreted. The discovery of fetal cfDNA in maternal circulation led to the development of non-invasive prenatal testing. ctDNA has been detected in cancer patients for over two decades and is now being used for non-invasive cancer diagnosis. ctDNA analysis can be used at various stages of cancer management, including diagnosis, treatment monitoring, and identification of resistance mutations. It can also be used for early diagnosis and screening. ctDNA analysis is transitioning from research to clinical use, with regulatory approvals for specific indications. The US Food and Drug Administration and the European Medicines Agency have approved ctDNA tests when tumour tissue is not available. Larger studies are underway to evaluate the performance and clinical utility of these tests. ctDNA analysis has shown potential in detecting mutations and monitoring clonal evolution. It can be used for non-invasive cancer classification and subtyping. However, technical and biological challenges remain in detecting mutant DNA in plasma and interpreting results. The presence of ctDNA in pre-symptomatic individuals suggests its potential for early diagnosis. ctDNA analysis can provide quantitative information on disease burden and genomic analysis. It is also useful for monitoring minimal residual disease and recurrence. The biology of cfDNA and ctDNA is still not fully understood, and further research is needed to explore their mechanisms of release, degradation, and representation in plasma. The stability of cfDNA fragments can be influenced by association with cell membranes, extracellular vesicles, or proteins. ctDNA is shorter than non-mutant cfDNA and is often detected in plasma. Animal experiments have shown that ctDNA can be used to interrogate tumour-derived DNA. ctDNA analysis can be used for various applications, including mutation detection, genomic profiling, and monitoring of disease progression. The sensitivity of ctDNA analysis can be improved through various techniques, such as digital PCR, single-base extension, and hybrid-capture sequencing. These methods allow for the detection of mutations at low allele fractions. ctDNA analysis can be used for early diagnosis of cancer, as mutations can be detected in plasma up to two years before diagnosis. It has also been used for the detection of early-stage cancers, such as ovarian and colorectal cancer. ctDNA analysis can be used for non-invasive molecular profiling, which is useful for stratifying patients in clinical trials. ctDNA analysis can also be used for monitoring treatment response and resistance. It can detect changes in ctDNA levels in response to therapy and may identify resistance mutations before clinical progression. ctDNA analysis can be used for longitudinal monitoring of cancer patients, including minimal residual disease and recurrence. It can also be used for adaptive therapy, where resistance mutations are identified and therapy is adjusted in real-time. The future of ctDNA analysis is promising, with ongoing research and clinical trials evaluating its utility in cancer management. ctLiquid biopsies, particularly circulating tumour DNA (ctDNA), are becoming increasingly important in cancer management. ctDNA is released into the bloodstream through cell death and may also be actively secreted. The discovery of fetal cfDNA in maternal circulation led to the development of non-invasive prenatal testing. ctDNA has been detected in cancer patients for over two decades and is now being used for non-invasive cancer diagnosis. ctDNA analysis can be used at various stages of cancer management, including diagnosis, treatment monitoring, and identification of resistance mutations. It can also be used for early diagnosis and screening. ctDNA analysis is transitioning from research to clinical use, with regulatory approvals for specific indications. The US Food and Drug Administration and the European Medicines Agency have approved ctDNA tests when tumour tissue is not available. Larger studies are underway to evaluate the performance and clinical utility of these tests. ctDNA analysis has shown potential in detecting mutations and monitoring clonal evolution. It can be used for non-invasive cancer classification and subtyping. However, technical and biological challenges remain in detecting mutant DNA in plasma and interpreting results. The presence of ctDNA in pre-symptomatic individuals suggests its potential for early diagnosis. ctDNA analysis can provide quantitative information on disease burden and genomic analysis. It is also useful for monitoring minimal residual disease and recurrence. The biology of cfDNA and ctDNA is still not fully understood, and further research is needed to explore their mechanisms of release, degradation, and representation in plasma. The stability of cfDNA fragments can be influenced by association with cell membranes, extracellular vesicles, or proteins. ctDNA is shorter than non-mutant cfDNA and is often detected in plasma. Animal experiments have shown that ctDNA can be used to interrogate tumour-derived DNA. ctDNA analysis can be used for various applications, including mutation detection, genomic profiling, and monitoring of disease progression. The sensitivity of ctDNA analysis can be improved through various techniques, such as digital PCR, single-base extension, and hybrid-capture sequencing. These methods allow for the detection of mutations at low allele fractions. ctDNA analysis can be used for early diagnosis of cancer, as mutations can be detected in plasma up to two years before diagnosis. It has also been used for the detection of early-stage cancers, such as ovarian and colorectal cancer. ctDNA analysis can be used for non-invasive molecular profiling, which is useful for stratifying patients in clinical trials. ctDNA analysis can also be used for monitoring treatment response and resistance. It can detect changes in ctDNA levels in response to therapy and may identify resistance mutations before clinical progression. ctDNA analysis can be used for longitudinal monitoring of cancer patients, including minimal residual disease and recurrence. It can also be used for adaptive therapy, where resistance mutations are identified and therapy is adjusted in real-time. The future of ctDNA analysis is promising, with ongoing research and clinical trials evaluating its utility in cancer management. ct