Aptamers are single-stranded oligonucleotides with great versatility, acting as therapeutic molecules with anticancer properties but also as delivery systems. A growing number of studies showed that aptamers can be properly designed to recognize a specific target, to conjugate drugs, nanoparticles or nucleic acid therapeutics (NATs) and to cross the blood brain barrier. In this review, we summarized the main advantages of aptamers as delivery system, focusing our attention on aptamer-mediated delivery of therapeutic oligonucleotides in glioblastoma. Glioblastoma represents the most common and aggressive primary malignant brain tumor in adults, with a median survival ranging from 14.6 to 20.5 months. Currently, the standard treatment of newly diagnosed tumor includes surgical resection followed by radiotherapy and chemotherapy with the alkylating agent temozolomide. However, the overall efficacy is limited and most patients relapse within a few months, calling attention on the development of alternative therapeutic strategies. Particularly, we discussed research studies on NAT delivery mediated by aptamer chimeras and aptamer-nanoparticle complexes able to impair various processes involved in glioblastoma tumorigenesis. This overview will help to highlight how aptamers, thanks to their advantages, could represent a promising tool for the development of innovative therapeutic approaches for glioblastoma treatment.