The need for precise and flexible synthetic methodology to underpin modern research in chemical biology and materials science has fuelled a resurgence of interest in Huisgen 1,3-dipolar cycloaddition chemistry. Of late, the in vogue chemistry for the assembly of complex biological molecules and specialist materials has been the copper-catalysed azide alkyne cycloaddition (CuAAC) reaction. However, in certain circumstances aversion to the copper catalyst flaws this approach and alternatives have been sought. Click chemistry has developed beyond the original triazole-forming trick and azides are no longer the only dipoles pursued as click cycloaddition partners. This article reviews some of the complications of the CuAAC reaction and evaluates the potential of nitrile oxide/alkyne cycloaddition (NOAC) as a covalent conjugation tool. With a focus on applications in nucleic acid chemistry and materials science it presents the case for a prominent position for nitrile oxides in the catalyst-free bioconjugation toolbox.