Heinz Josef Lenz, MD, FACP, University of Southern California (USC), Los Angeles, CA, discusses the key challenges of using liquid biopsy in the diagnosis and treatment of colorectal cancer. Access to tests is a large consideration, as this varies in healthcare systems around the world. There are also differences in the types of liquid biopsies that are performed, including tissue-informed vs tissue-uninformed liquid biopsy. Prof. Lenz discusses the challenge of the highly sensitive nature of the technology and proposes that future research can work on using liquid biopsy to successfully identify early recurrence and minimum residual disease (MRD) in patients. This interview took place at the International Society of Liquid Biopsy (ISLB) 2021 Virtual Meeting.