Over the years, there has been a treatment paradigm shift for patients with metastatic colorectal cancer with the emergence of the concept of "Continuum of Care" as optimal palliative therapy strategy. This concept is reflected in the induction-maintenance approach in first-line therapy, which is meant to prolong the duration of tumor-directed therapy while mitigating treatment-related toxicities. Traditionally, maintenance chemotherapy refers to the utilization of regimens with less toxicity after the initial upfront treatment. The need for this rose over the years because of significantly improved survival of patients with metastatic colorectal cancer. The classic study using the principles of maintenance chemotherapy options is illustrated well in the recently published CAIRO-3 study by the Dutch Colorectal Cancer Group. There is still an unmet need. Using novel agents alone or in various combinations with biologics through trials utilizing clinically relevant endpoints and efficient clinical trial designs are important considerations.