Instances of explanatory reduction are often advocated on metaphysical grounds; given that the only real things in the world are subatomic particles and their interaction, we have to try to explain everything in terms of the laws of physics. In this paper, we show that explanatory reduction cannot be defended on metaphysical grounds. Nevertheless, indispensability arguments for reductive explanations can be developed, taking into account actual scientific practice and the role of epistemic interests. Reductive explanations might be indispensable to address some epistemic interest answering a specific explanation-seeking question in the most accurate, adequate and efficient way. Just like explanatory pluralists often advocate the indispensability of higher levels of explanation pointing at the pragmatic value of the explanatory information obtained on these higher levels, we argue that explanatory reduction—traditionally understood as the contender of pluralism—can be defended in a similar way. The pragmatic value reductionist, lower level explanations might have in the biomedical sciences and the social sciences is illustrated by some case studies.