The development of minimally invasive tests for cancer diagnosis and prognosis will aid in the research of new treatments and improve survival rates. Liquid biopsies seek to derive actionable information from tumor material found in routine blood samples. The relative scarcity of tumor material in this complex mixture makes isolating and detecting cancerous material such as proteins, circulating tumor DNA, exosomes, and whole circulating tumor cells a challenge for device engineers. This review describes the chemistry and applications of branched and hyperbranched to improve the performance of liquid biopsy devices. These polymers can improve the performance of a liquid biopsy through several mechanisms. For example, polymers designed to increase the affinity of capture enhance device sensitivity. On the other hand, polymers designed to increase binding avidity or repel nonspecific adsorption enhance device specificity. Branched and hyperbranched polymers can also be used to amplify the signal from small amounts of detected material. The further development of hyperbranched polymers in liquid biopsy applications will enhance device capabilities and help these critical technologies reach the oncology clinic where they are sorely needed. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices.