The institutional structure of legal enforcement may influence the substantive evolution of a discipline. US antitrust is a clear example in this regard. It is widely accepted that some of its institutional features explain the distinct direction that the field has taken on the other side of the Atlantic. The enforcement architecture in the EU is different. However, no systematic effort has been undertaken to make sense of how it has influenced the substantive dimension of the discipline in Europe. The ambition of this monograph is to make sense of this question. In particular, it seeks to identify patterns in the behaviour of the European Commission – around which enforcement, and thus necessarily the substantive interpretation of the provisions, has by and large revolved – and of the EU courts. The preferences of the European Commission as an administrative authority are inevitably reflected in the cases it chooses and in the way in which it crafts the legal provisions. The conclusions are drawn from a systematic and comprehensive analysis of the case law and administrative practice engaging with the notion of restriction of competition under Article 101 TFEU, that of abuse under Article 102 TFEU and, finally, with the substantive criterion under the successive Merger Regulations.