The guest editors believe that this special section and the parallel special section in Neurophotonics are valuable reading for scientists both inside and outside the biomedical optics community. Readers will get a glimpse of how NIRS technologies impact medicine today and what can be expected from developments of tomorrow’s technologies. In the coming years, current generations of NIRS instruments will migrate along the translational path toward clinical adoption as both the product engineering and use protocols are refined. However, while many aspects of NIRS technology have been tested for limits such as resolution, quantitative accuracy, field-of-view, depth sensitivity, wearability, portability, and integration with other modalities—many of these individual demands are at odds with other performance measures. For example, the solutions to several performance specifications positively correlate with instrument weight and thus work against wearability. Thus the phase-space for optimizing and engineering real-world NIRS instruments remains immense. In summary, NIRS has already provided many valuable insights in clinical research. While NIRS is on the verge of entering everyday clinical routine, the innovation yet to come is still brighter.