Glioblastoma (GBM) is the most common and aggressive primary brain tumors in adults. Despite being one of the most genetically and molecularly characterized tumors, patient prognosis remains dismal. Many factors have contributed to the challenges of developing effective clinical therapies, such as tumor heterogeneity, immune-suppressive microenvironment, and therapy resistance. From the perspective of therapeutics delivery, one of the main obstacles is to get newly discovered therapeutic agents across the blood-brain barrier (BBB) to penetrate the brain parenchyma. In this context, this book chapter provides an overview of three different strategies of delivering antitumor agents intended to circumvent the BBB and highlight the strengths and weakness of each approach.