Infrared (IR) spectroscopy is at the cross-roads, with the requirement to compete with cutting-edge technologies in biosciences, mostly based on analytical performances dealing with the super-resolutions: time, lateral/spatial, and contrast. IR microscopy is diffraction limited in most cases, thus not accessing to high lateral/spatial resolutions. Additionally, it has a poor signal-to-noise ratio on a single scan, thus requiring long-lasting acquisitions that are not suitable to analyze ns-lasting biochemical events. However, it is unique because it provides a broad global chemical information of the sample contents. It is also unique because it does not require heavy sample preparation nor labeling and can be coupled to other techniques (multimodality). Finally, it is again unique because it provides quantitative measurements, thus suitable for 1D to 4D data exploitation procedures. This short review shows that IR spectroscopy will be certainly subjected to a second century of innovations, maintaining its influence in the panorama of cutting-edge analytical techniques.