Thermodynamic and kinetic studies complement high-resolution structures of G-quadruplexes. Such studies are essential for a thorough understanding of the mechanisms that govern quadruplex folding and conformational changes in quadruplexes. This perspective article reviews representative thermodynamic and kinetic studies of the folding of human telomeric quadruplex structures. Published thermodynamic data vary widely and are inconsistent; possible reasons for these inconsistencies are discussed. The key issue of whether such folding reactions are a simple two-state process is examined. A tentative energy balance for the folding of telomeric quadruplexes in Na(+) and K(+) solution, and for the conformational transition between these forms is presented.