Proton detection developed in the last 20 years as the method of choice to study biomolecules in the solid state. In perdeuterated proteins, proton dipolar interactions are strongly attenuated, which allows yielding of high-resolution proton spectra. Perdeuteration and backsubstitution of exchangeable protons is essential if samples are rotated with MAS rotation frequencies below 60 kHz. Protonated samples can be investigated directly without spin dilution using proton detection methods in case the MAS frequency exceeds 110 kHz. This review summarizes labeling strategies and the spectroscopic methods to perform experiments that yield assignments, quantitative information on structure, and dynamics using perdeuterated samples. Techniques for solvent suppression, H/D exchange, and deuterium spectroscopy are discussed. Finally, experimental and theoretical results that allow estimation of the sensitivity of proton detected experiments as a function of the MAS frequency and the external B0 field in a perdeuterated environment are compiled.