Model-Driven Engineering (MDE) is a software engineering discipline which promotes a new way to develop and maintain software systems by using models as the primary artifacts of the engineering process. The relevance of such a discipline is evidenced by the increasing interest in many scientific endeavors, active technology projects (e.g., the Eclipse Modeling Project1) and numerous industrial projects ranging from direct applications of MDE concepts and tools, to those developing its foundations. Historically model transformations and code generation from abstract models have been among the most prominent MDE applications. Nevertheless, they represent only a partial coverage of the MDE application potential: recent advances inMDEhave shownhowmodel differencing techniques,modelmanagement,megamodeling and interoperability are equally relevant to leverage the discipline of MDEwhile gaining acceptance, or becoming a mainstream industry practice. While anecdotal descriptions of MDE case studies, as well as new developments in tools, theories and technology appear throughout the literature, success stories of MDE application infrequently appear. This may be due to the many open and unresolved research issues in MDE (e.g., how to deal with very large models, designing model management tool chains), despite the relativematurity achieved by a number of tools—particularly those formodel transformation. Many researchers tend to focus on investigating conceptual if not theoretical aspects of MDE, deprecating the relevance of the assessment of the overall discipline in terms of its application to real scale and complexity scenarios. While such robust theoretical contributions are of substantial importance, applications emerging from themost disparate domains may reveal new directions for development of the theory as well as lessons of transferable value for future MDE practice. IfMDE ismoving frombeing an emerging technology to becoming a standard software engineering practice, thenweneed to demonstrate evidence. We believe that flavors of MDE are now mainstream, and this special issue intends to evidence this claim. For this special issue, we selected contributions which show howMDE techniques can be successfully applied in practice showing experiences and providing insights on issues encountered when applying these approaches in practice.