Near-infrared (NIR) light, within the 700-1000 nm therapeutic optical window, offers deep tissue penetration, low photocytotoxicity, and minimal side effects, making it ideal for remote control of biocompatible reactions in vivo. This review explores recent advances in NIR-triggered reactions, focusing on direct and indirect activation strategies. Direct approaches utilize NIR-responsive protecting groups, while indirect methods employ upconversion materials and photocatalysis to overcome NIR's energy limitations. These innovations expand noninvasive in vivo control capabilities. Applications include NIR-mediated drug delivery, biological molecule activation, and proximity labeling for protein interaction studies. Such reactions enable precise modulation of biological events under native conditions. The review highlights the potential of integrating advanced nanomaterials and optimizing indirect activation techniques to enhance reaction efficiency. It also emphasizes the requirement for interdisciplinary collaboration to refine NIR-responsive systems and facilitate clinical translation. By showcasing state-of-the-art NIR-controlled chemistry and identifying key areas for future research, this work aims to inspire advancements in biomedical research and therapeutics. Addressing the challenges of in vivo chemical control, this review positions NIR chemistry as a critical component in the evolution of biocompatible reaction methodologies.