The hydrazine group serves as a great anchor for bioconjugation; however, the application of hydrazone ligation has been limited by poor product stability. We aim to resolve such issues by optimizing the recently established pyrazolone ligation and investigating a new pyrazole ligation. We have identified a new, electron-deficient pyrazolone ligation and a regiospecific pyrazole ligation, both offering aqueous buffer stable and chemically inert products possessing triazole-like structures while not involving any heavy metal catalyst.