Metronomic scheduling of anticancer treatment (MSAT) is progressively gaining interest after the antiangiogenic properties of metronomic chemotherapy and its potential to overcome drug resistance was initially described in 2000. MSAT has now grown beyond the anticipated scope of antiangiogenic chemotherapy, with accumulating evidence demonstrating that these treatments may also act by stimulating an antitumor immune response and could ultimately lead to reinduction of tumor dormancy. An increasing number of drugs, not initially developed as anticancer agents, are currently being used in metronomic protocols in order to increase treatment efficacy. Interestingly, these ’repositioned’ agents can target cancer cells, the tumor vasculature or, more broadly, the tumor microenvironment. Malignant tumors are no longer regarded as simple congregations of cancer cells but as genuine tissues with various components such as blood vessels, fibroblasts, inflammatory cells and an extracellular matrix. These different components and their multiple interactions play a crucial role in tumor development and response to treatment. Therefore, future anticancer treatments will have to take into account the tumor microenvironment and aim to target the different cellular and molecular participants encompassed in a tumor, as well as their specific interactions. In this article, we explain why MSAT represents a very attractive strategy for developing next-generation multitarget therapies.