There is tremendous interest in the use of fluorogenic reactions for detecting and imaging nucleic acids, especially specific DNA and RNA sequences. Applications include time-resolved imaging of transcription, detection of disease-related single nucleotide polymorphisms, and tracking RNA fragments such as microRNAs. Despite advances in the use of molecular beacons, aptamers and antisense agents, the rapid detection and imaging of oligonucleotides in live cells and physiologically relevant media remains challenging. Current methods, although powerful, suffer from numerous drawbacks. For example, previous ligation reactions have been hampered by slow kinetics and autohydrolysis, often relying on nucleophilic/electrophilic reactions, which allow cellular or solvent nucleophiles to compete for reactivity. Fluorogenic bioorthogonal ligations offer a promising route towards the fast and robust fluorescent detection of specific DNA or RNA sequences. Tetrazine bioorthogonal cycloadditions benefit from rapid tunable reaction rates and high stability against hydrolysis in buffer and serum. Furthermore, tetrazines act as both a fluorescent quencher and a reactive group, minimizing the complexity of fluorogenic ligation probe design.