The ability to assess minimal residual disease (MRD) through circulating tumor DNA (ctDNA) is revolutionary within oncology as it provides the most precise modality for identifying residual cancer post curative therapies. This review examines the advancements in the technologies for ctDNA-based MRD detection published from the year 2020 to present while briefly mentioning the technologies developed prior as a reference for the time line. This review explains the transformation of the older PCR-based technologies to next generation sequencing technologies which include digital PCR, tumor-informed assays like CAPP-seq, and novel technologies that analyze the tumor epigenome and fragmentome as well. All of these technologies demonstrate the increasing ability of the practitioner to identify and monitor cancer during treatment to custom the treatment and therapy to the patient. From the treatment of various different cancers there is specific disease, treatment and therapy monitoring and customizing available to the practitioner. However, there are still numerous issues such as standardization, analytical validation and routine clinical integration of the technology remain. This review aims to describe the available technologies, their integration within the clinical paradigm, assess their value and technologies and forecast the prospective of ctDNA MRD surveillance.