Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Although the overall incidence is less than 10 per 100,000 individuals, its poor prognosis and low survival rate make GBM a crucial public health issue. The main challenges for GBM treatment are related to tumor location and its complex and heterogeneous biology. In this sense, a broad range of nanoparticles with different sizes, architectures, and surface properties, have been engineered as brain drug delivery systems. Among them, lipid-based nanoparticles, such as liposomes, have been pointed out as promising materials to deliver antitumoral drugs to the central nervous system and thus, to improve brain drug targeting and therapeutic efficiency. Here, we describe the synthesis and general characteristics of lipid-based nanoparticles, as well as evidence in the past 5 years regarding their potential use to treat GBM.