High-resolution solid-state NMR (SSNMR) of paramagnetic systems has been largely unexplored because of various technical difficulties due to large hyperfine shifts, which have limited the success of previous studies through depressed sensitivity/resolution and lack of suitable assignment methods. Our group recently introduced an approach using “very fast” magic angle spinning (VFMAS) for SSNMR of paramagnetic systems, which opened an avenue toward routine analyses of small paramagnetic systems by 13C and 1H SSNMR [Y. Ishii et al., J. Am. Chem. Soc. 125, 3438 (2003); N. P. Wickramasinghe et al., ibid. 127, 5796 (2005)]. In this review, we discuss our recent progress in establishing this approach, which offers solutions to a series of problems associated with large hyperfine shifts. First, we demonstrate that MAS at a spinning speed of 20 kHz or higher greatly improves sensitivity and resolution in both 1H and 13C SSNMR for paramagnetic systems such as Cu(II)(DL-alanine)2·H2O (Cu(DL-Ala)2) and Mn(acac)3, for which the spectral dispersions due to 1H hyperfine shifts reach 200 and 700 ppm, respectively. Then, we introduce polarization transfer methods from 1H spins to 13C spins with high-power cross polarization and dipolar insensitive nuclei enhanced by polarization transfer (INEPT) in order to attain further sensitivity enhancement and to correlate 1H and 13C spins in two-dimensional (2D) SSNMR for the paramagnetic systems. Comparison of 13C VFMAS SSNMR spectra with 13C solution NMR spectra revealed superior sensitivity in SSNMR for Cu(DL-Ala)2, Cu(Gly)2, and V(acac)3. We discuss signal assignment methods using one-dimensional (1D) 13C SSNMR 13C–1H rotational echo double resonance (REDOR) and dipolar INEPT methods and 2D 13C/1H correlation SSNMR under VFMAS, which yield reliable assignments of 1H and 13C resonances for Cu(Ala-Thr). Based on the excellent sensitivity/resolution and signal assignments attained in the VFMAS approach, we discuss methods of elucidating multiple distance constraints in unlabeled paramagnetic systems by combing simple measurements of 13C T1 values and anisotropic hyperfine shifts. Comparison of experimental 13C hyperfine shifts and ab initio calculated shifts for α- and β-forms of Cu(8-quinolinol)2 demonstrates that 13C hyperfine shifts are parameters exceptionally sensitive to small structural difference between the two polymorphs. Finally, we discuss sensitivity enhancement with paramagnetic ion doping in 13C SSNMR of nonparamagnetic proteins in microcrystals. Fast recycling with exceptionally short recycle delays matched to short 1H T1 of ∼60 ms in the presence of Cu(II) doping accelerated 1D 13C SSNMR for ubiquitin and lysozyme by a factor of 7.3–8.4 under fast MAS at a spinning speed of 40 kHz. It is likely that the VFMAS approach and use of paramagnetic interactions are applicable to a variety of paramagnetic systems and nonparamagnetic biomolecules. [ABSTRACT FROM AUTHOR]