The intranasal drug delivery route provides exciting expectations regarding the application of engineered nanomaterials as nano-medicines or drug-delivery vectors into the brain. Among nanomaterials, multiwalled CNTs (MWCNTs) are some of the best candidates for brain cancer therapy since they are well known to go across cellular barriers and display an intrinsic ability to block cancer cell proliferation triggering apoptosis. This study reveals that microglial cells, the brain macrophages and putative vehicles for MWCNTs into the brain, undergo a dose-dependent cell division arrest and apoptosis when treated with MWCNTs. Moreover, it is shown that MWCNTs severely interfere with both cell migration and phagocytosis in live microglia. These results lead to a re-evaluation of the safety of inhaled airborne CNTs and provide strategic clues of how to biocompatibilize MWCNTs to reduce brain macrophage damage and to develop new nanodrugs.