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This proceedings volume combines review articles that summarize research executed at the Munich Centre of Advanced Computing (MAC) from 2008 to 2012. the articles address the increasing gap between what should be possible in Computational Science and Engineering due to recent advancements in algorithms, hardware, and networks, and what really can be achieved in practice, on novel computing architectures, where computation itself is a multifaceted process, with hardware awareness or ubiquitous parallelism due to many-core systems being just two of the challenges. Topics cover both the methodological aspects of advanced computing (algorithms, parallel computing, data exploration, software engineering) and leading-edge applications from chemistry, geosciences, civil and mechanical engineering, etc., reflecting the highly interdisciplinary setup of the Munich Centre of Advanced Computing.