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Abstract Information and communication technology (ICT) is getting smaller and faster at a dashing pace and is increasingly pervading production technology. This penetration of ICT within and across production technology enables companies to aggregate and utilize massive amounts of data of production processes, both horizontally (across different products) and vertically (from machine level, over the shop floor, to the supply chain level). Presumably, this yields in Smart Factories with adaptable manufacturing processes that adjust to different goals, such as performance, product quality, or resource efficiency. But the increasing amount of available data also raises considerable challenges: Strategic decisions still depend on humans in the loop who have to perceive and process increasingly complex multi dimensional data sets and to make decisions whose effects are increasingly difficult to forecast. This paper is concerned with the potential of the human factor. Along with three case studies, we demonstrate the potential of human factors in the development of applications for Smart Factories and enterprises in the era of Industry 4.0. The paper concludes with a set of guidelines and methods for the usercentred development of applications for Industry 4.0.