Over the course of the last three decades, computer simulations have become a major tool of doing science and engaging with the world, not least in an effort to predict and intervene in a future to come. Born in the context of the Second World War and the discipline of physics, simulations have long spread into most diverse fields of enquiry and technological application. This paper introduces a topical collection focussing on simulations in the life sciences. Echoing the current state of tinkering, fast developments, segmentation of knowledge and interdisciplinary collaboration, and in an effort to bridge the science-humanities divide, the contributors to this collection come from multiple disciplinary backgrounds, including information studies, cognitive sciences, philosophy and biology. The ambiguous character of simulations, their cutting across scientific disciplines, analysis and prediction, understanding and doing, gave rise to their success in contemporary life sciences and has been the object of much scientific debate. One of the main aims of this topical collection, by contrast, is to call into question the assumption of an obvious use and easy transfer of methods between fields of knowledge as diverse as, e.g. physics and biology. The collection presents historical case studies from various biological sub-fields. The articles study how simulations are used and the ways they contribute specifically to our understanding of life. Taking up Sergio Sismondo's description of simulations as compromises and glue, they also critically engage with the question of what exactly the life sciences have been gluing together over the last two decades.