Aptamers are nonnaturally occurring oligonucleotides generated by the SELEX (Systematic Evolution of Ligands by Exponential enrichment) process. Due to their unique three-dimensional structures, aptamers can bind to various targets, ranging from small compounds to cells and tissues, with high affinity and specificity. While first reported in 1990, aptamers have become useful tools in the biomedical field because of their unique characteristics, such as easy and quick preparation, cost-effectiveness, small size, versatility, et al. Recently various chemical modifications have been introduced to enhance aptamer's stability in the body fluids and their bioavailability in animals, which have pushed aptamer closer to therapeutic and diagnostic application. This review provides an overview of the aptamer modifications and their application in the nervous system disorders.