In a recent paper in Cambridge Quarterly of Healthcare Ethics on the necessary conditions for morally responsible animal research David DeGrazia and Jeff Sebo claim that the key requirements for morally responsible animal research are (1) an assertion of sufficient net benefit, (2) a worthwhile-life condition, and (3) a no-unnecessary-harm condition. With regards to the assertion (or expectation) of sufficient net benefit (ASNB), the authors claim that morally responsible research offers unique benefits to humans that outweigh the costs and harms to humans and animals. In this commentary we will raise epistemic, practical, and ethical challenges to DeGrazia and Sebo’s emphasis on benefits in the prospective assessment of research studies involving animals. We do not disagree with DeGrazia and Sebo that, at the theoretical level, the benefits of research justify our using animals. Our contribution intends to clarify, at the practical level, how we should understand benefits in the prospective assessment and moral justification of animal research. We argue that ASNB should be understood as an assessment of Expectation of Knowledge Production (EKP) in the prospective assessment and justification of animal research. EKP breaks down into two further claims: (1) that morally responsible research generates knowledge worth having and (2) that morally responsible research is designed and executed to produce generalizable knowledge. We understand the condition called knowledge worth having as scientists’ testing a hypothesis that, whether verified or falsified, advances an important interest, and production of generalizable knowledge in terms of scientific integrity. Generalizable knowledge refers to experimental results that generalize to a larger population beyond the animals studied. Generalizable scientific knowledge is reliable, replicable, and accurately descriptive. In sum, morally responsible research will be designed and carefully executed to successfully test a hypothesis that, whether verified or falsified, advances important interests. Our formulation of EKP, crucially, does not require further showing that an experiment involving animals will produce societal benefits.