Derived by an iterative in vitro selection process termed Systematic Evolution of Ligands by EXponential enrichment (SELEX), aptamers are short single-stranded oligonucleotides that bind to their cognate targets with high affinity and selectivity. Generally, aptamers have been widely used in biological and pre-clinical medical applications. A comprehensive analysis of aptamer selection data maintained in the Aptamer Database identified factors that should be carefully considered upon the design of selection experiments to optimize success. These findings should be applied to selections for nervous system related targets to improve the quality of selected aptamers. Specifically, the nervous system presents an especially interesting field of investigation. For example the aptamer target thrombin is a protein involved in the coagulation cascade and has important relevancy for stroke. The development of an aptamer-based pH-driven DNA nanomachine (pHAST) for the specific catch-and-release of thrombin is described. This work is an important example of how existing aptamers could be incorporated into a nanodevice to add specific functionality for applications within the nervous system. Dopamine is a small molecule neurotransmitter implicated in mental illness and neurodegenerative disease. The ability of dopamine-binding aptamers to attenuate perseveration and locomotor behaviour associated with dopamine over-activity was shown in live rodents. Finally, an aptamer-gold nanoparticle based sensor was developed based on a dopamine binding aptamer, DopaA20min, identified from a novel selection.