Forty years ago, we learned of the major double helical structure adopted by DNA. It combined both elegance and simplicity in its design. Since then we have learned that DNA can also adopt other conformations. We now know that it can exist in a variety of triple-stranded and quadruple-stranded forms, as well as forms that are left-handed. The list of alternative conformations that can be adopted by this molecule is still growing. These conformations represent a major biological challenge to understand their role in biological systems. This type of work represents an active frontier in molecular biology today.