Physicists have often in history turned their attention to the phenomena of life. They’ve been attracted to biology for several reasons such as the use of technologies of physics to study biology, the expectation that living matter could be reduced to physical principles or the appeal of a science of life after the military use of atomic energy. My project investigates the circumstances under which physicists approach biological problems both from historical and contemporary perspectives. The present paper comprises my project’s contemporary part, which investigates the current influx of physicists into the field of biology and I use oral history as one of the methodological tools. I interviewed physicists who work on biological problems in those areas concerned with systems, dynamics and the organization of the cell, particularly systems biology. In the context of the post-genomic era, the scientific challenge of converting data into knowledge is dependent on high-throughput technologies and computational modelling, which increase the need for interdisciplinary collaboration (cf. Keller 2002). Because of its interdisciplinarity, the field of systems biology has been subject of sociological investigation (e.g. Calvert & Fujimura 2012) and our analysis focuses on the physicists that are, one more time in history, playing a central role in biological research. Up to now, I interviewed and recorded research group leaders and postdoctoral researchers from Germany, Israel and Brazil. The results are also based on visits to laboratories, observations of interdisciplinary interactions, meetings, informal conversation and e-mail exchanges, as well as the scientific, historical and theoretical literature. In the discussion, I focus on epistemological issues derived from the interdisciplinary environment, such as cultural gaps between the disciplines and the modelling strategies.