Soft ionization methods produce closed-shell ions. MS/MS of these ions is classically performed using collision-induced dissociation. The resulting spectra often lack enough information to elucidate a molecular structure, the loss of small neutral molecules being the lowest energy fragmentation channels. Alternative methods have been developed to increase the number of structurally informative ions. Activation techniques using electrons, photons, and hydrogen radicals have demonstrated their complementarity for optimized MS/MS strategies. Besides fragmentation, alternative activation methods can provide information about tertiary structure, as well as spectroscopic data on biomolecular ions in the gas phase. Electron photodetachment, with or without subsequent dissociation, can be used to probe how the action of photons depends on their wavelength. Here, the aforementioned methods will be reviewed with an emphasis on those allowing radical fragmentation pathways.