The blood¿brain barrier (BBB) protects the central nervous system (CNS) from toxins and homeostatic disruptions. However, this barrier also prevents nearly 100% of therapeutics from entering the CNS. The advent of nanoscale drug carriers, in particular metallic-based nanoparticles, shows significant promise to overcome this barrier. These nanoparticles can be synthesized from a number of materials which can be assessed to determine characteristics such as size, morphology, and surface properties. Further, in vivo and in vitro models are both pivotal to evaluate properties including permeability of nanoparticles into the CNS, disruptions to BBB integrity, biodistribution, and toxicity. Such methods and models are critical to further our understanding of how different nanoparticle properties elicit distinct biological responses. These can be leveraged to advance the development of novel nanocarriers capable of crossing the BBB and delivering biological agents to the CNS.