The significant progresses recently achieved in the treatment of gastric, pancreatic and liver cancers have led clinicians to evaluate the opportunity to interrupt first-line treatments before disease progression and to consider maintenance therapies. In colorectal cancer, this strategy has produced remarkable advances, and patients whose disease is controlled after a few months of upfront therapy may derive clinical benefit and enjoy improved quality of life from continuing a less intensive treatment or early shifting to another, well-tolerated regimen. If the concept of maintenance may be applicable to other gastrointestinal malignancies is currently unknown, but the evidence is rapidly emerging.