This review celebrates the 30th anniversary of the first in vivo near-infrared (NIR) spectroscopy (NIRS) publication, which was authored by Professor Frans Jöbsis. At first, NIRS was utilized to experimentally and clinically investigate cerebral oxygenation. Later it was applied to study muscle oxidative metabolism. Since 1993, the discovery that the functional activation of the human cerebral cortex can be explored by NIRS has added a new dimension to the research. To obtain simultaneous multiple and localized information, a further major step forward was achieved by introducing NIR imaging (NIRI) and tomography. This review reports on the progress of the NIRS and NIRI instrumentation for brain and muscle clinical applications 30 years after the discovery of in vivo NIRS. The review summarizes the measurable parameters in relation to the different techniques, the main characteristics of the prototypes under development, and the present commercially available NIRS and NIRI instrumentation. Moreover, it discusses strengths and limitations and gives an outlook into the “bright” future.