Liquid biopsy, which includes both circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) has become a valuable tool for cancer diagnosis and monitoring. It offers a less invasive approach than traditional tissue biopsy and recent technological advancements have enabled their use in comprehensive analysis of tumor molecular characteristics. By capturing the dynamic nature of tumors through repeated sampling, liquid biopsy addresses the limitations of tissue biopsy and provides insights into tumor heterogeneity over time. It is being extensively studied in patients with advanced colorectal cancer because it can aid in diagnosis, predict disease course, and guide treatment selection. Furthermore, as personalized medicine becomes more common, identifying genetic changes that cause cancer cells to become resistant to treatment is crucial. This chapter explores the emerging field of liquid biopsy, with a particular focus on the role and potential of circulating tumor cells (CTCs) in the context of colorectal cancer.