Explanation and interpretation are two core theoretical scientific activities, and this chapter suggests a way of conceptualizing them and of normatively appraising them within the premises of a comparative approach. There are many distinct activities taking place in the scientific process, but explanation is widely considered as the core theoretical activity since it is an epistemic activity in which representation and inferential reasoning are merged in a complex way in order to enlighten natural, biological and social phenomena. However, there is another core theoretical activity directed towards other goals that is equally complex: interpretation. This is the activity that deals with meaningful material. The importance of interpretation is standardly stressed in the humanities, but there is no reason to assume that this epistemic activity should be normatively appraised according to different standards than explanation. It is indeed the claim of this chapter that there is no dichotomy of science and humanities at the methodological level and that the same normative approach can be successfully applied to both areas, notwithstanding a series of important differences.