The Cu(i)-catalyzed azide and alkyne 1,3-dipolar cycloaddition (CuAAC), commonly known as the "click reaction", has emerged as a powerful and versatile synthetic tool that finds a broad spectrum of applications in chemistry, biology and materials science. The efficiency, selectivity and versatility of the CuAAC reactions have enabled the preparation of vast arrays of triazole compounds with biological and pharmaceutical applications. In this feature article, we outline the applications and future prospects of click chemistry in the synthesis and development of small molecules that target G-quadruplex nucleic acids and show promising biological activities. Furthermore, this article highlights the template-assisted in situ click chemistry for developing G-quadruplex specific ligands and the use of click chemistry for enhancing drug specificity as well as designing imaging and sensor systems to elucidate the biological functions of G-quadruplex nucleic acids in live cells.