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This proceedings volume collects review articles that summarize research conducted 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 advances in algorithms, hardware, and networks, and what can actually be achieved in practice; they also examine 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 faced. Topics cover both the methodological aspects of advanced computing (algorithms, parallel computing, data exploration, software engineering) and cutting-edge applications from the fields of chemistry, the geosciences, civil and mechanical engineering, etc., reflecting the highly interdisciplinary nature of the Munich Centre of Advanced Computing.