The critical role of nucleic acids, DNA and RNA, is to store and process genetic information that includes all needs for life. The Human Genome Project (HGP) showed that about 98% of the human genome does not code for protein expression, and the role of these noncoding sequences remains unknown. The HGP also showed that repetitive DNA sequences, including dinucleotide repeats, trinucleotide repeats, and telomeric, and centromeric sequences, are widely distributed in the human genome. Most of the repetitive DNA potentially can fold into noncanonical structures via both Watson-Crick and non-Watson-Crick base pairs. These structures should have discernible conformational signals in nucleic acid-nucleic acid, nucleic acid-protein, and nucleic acid-drug interactions. The structural polymorphism of these nucleic acids is generated by not only their sequence but also by their surrounding conditions. In this review, the characteristics of the nucleic acid structures, their thermodynamic and kinetic properties, and their importance in pharmacology and medicine will be discussed.