Neutrinos are the only particles in the Standard Model that could be Majorana fermions, that is, completely neutral fermions that are their own antiparticles. The most sensitive known experimental method to verify whether neutrinos are Majorana particles is the search for neutrinoless double-beta decay. The last 2 decades have witnessed the development of a vigorous program of neutrinoless double-beta decay experiments, spanning several isotopes and developing different strategies to handle the backgrounds masking a possible signal. In addition, remarkable progress has been made in the understanding of the nuclear matrix elements of neutrinoless double-beta decay, thus reducing a substantial part of the theoretical uncertainties affecting the particle–physics interpretation of the process. On the other hand, the negative results by several experiments, combined with the hints that the neutrino mass ordering could be normal, may imply very long lifetimes for the neutrinoless double-beta decay process. In this report, we review the main aspects of such process, the recent progress on theoretical ideas and the experimental state of the art. We then consider the experimental challenges to be addressed to increase the sensitivity to detect the process in the likely case that lifetimes are much longer than currently explored, and discuss a selection of the most promising experimental efforts.