Surface chemistry is a critical, yet underdeveloped topic in SERS. The surface landscape and associated thermodynamic equilibria of the most common SERS colloids are here reviewed to provide key, centralized information to push the technique forward.

In the wake of a global, heightened interest towards biomarker and disease detection prompted by the SARS-CoV-2 pandemic, surface enhanced Raman spectroscopy (SERS) positions itself again at the forefront of biosensing innovation. But is it ready to move from the laboratory to the clinic? This review presents the challenges associated with the application of SERS to the biomedical field, and thus, to the use of excitation sources in the near infrared, where biological windows allow for cell and through-tissue measurements. Two main tackling strategies will be discussed: (1) acting on the design of the enhancing substrate, which includes manipulation of nanoparticle shape, material, and supramolecular architecture, and (2) acting on the spectral collection set-up. A final perspective highlights the upcoming scientific and technological bets that need to be won in order for SERS to stably transition from benchtop to bedside.