The book investigates the long-standing question of whether and, if yes, how insights from theories of reference could be integrated into philosophical theories of science. Although the views on this matter were not always clear-cut, two characteristic positions have been crystallized through the past decades. Anti-referentialist philosophers of science denied the theoretical importance of the phenomenon of reference. They decidedly rejected the relevance of linguistic considerations for their inquiries. Their opponents, philosophers of science with linguistic inclinations, emphasized the significance of reference, mainly by pointing to the necessary world-connectedness of the technical terms of the language of science. The present study provides new arguments in defense of the latter position. The central claim is that, understood as a relational mechanism, reference plays a constitutive role in both our semantic and epistemic contact with the world. If this claim is correct, then it may be reasonably thought that some theses about reference are genuinely explanatory when we try to give a systematic picture about how scientists construe their theories and how science in general achieves its ends.