Isolation of circulating tumor cells (CTCs) from blood has long been a challenge due to the rarity and heterogeneity of these cells. Detection technologies have predominantly focused on different molecular or physical properties of CTCs. Size-based isolation approach using microfilters have been widely used to capture CTCs because of the difference in size and stiffness of the cells compared to other hemocytes. Isolation of rare cells based on their size was the original CTC enrichment technique and it demonstrated a simple yet rapid method that enhanced the recovery of cells with high throughput. In this review, we highlight key technical aspects of filter-based isolation, detection, and characterization of CTCs, and compare the clinical performance of filter-based devices with the approved platforms and immunoassays used for the analysis of CTCs. We have also discussed future prospective and incorporation of advances in immunochemistry technique into the filter-based platforms for enhancing the utility in clinical settings.