Despite great advances have been made in oncologic approaches, the morbidity and mortality caused by colon cancer are still overwhelming. Particularly, the intra-and inter-tumour heterogeneity makes accurate sampling challenging and often leads to failure of even modern therapeutic strategies. Moreover, tumour molecular genotype can suffer alterations over time, triggering suboptimal therapeutic outcomes as a result of irrelevant information provided by histological biopsies. Daily, tumour cells shed into the bloodstream at the early stages of the disease. These circulating tumour cells (CTCs) can be detected and analysed after enrichment, providing this way valuable information in real time. Furthermore, apoptotic and/or necrotic tumour cells discharge DNA fragments into the circulating bloodstream. Elevated levels of these so-called circulating tumour DNA (ctDNA) fragments can be identified in the peripheral blood of patients as compared to healthy individuals. In this view, the detection and characterization of the CTCs and ctDNA are a real-time "liquid biopsy" that has been developed for accurate tumour monitoring and molecular characterization. This modern non-invasive analytical approach allows consecutive sampling to monitor CTC number and tumour genetic changes over time without the need of tissue biopsy. Consequently, "liquid biopsies" can be used to screen for cancer, stratify patients to the optimum treatment and to monitor the patient's response to treatment or identify treatment resistance. This chapter offers an overview of the following approaches with respect to liquid biopsies: CTCs and ctDNA. Some of the analytical techniques and challenges in the detection of these rare events will also be presented here.