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The era of Big Data is claimed to herald the end of hypothesis‐driven research in favour of sophisticated algorithms uncovering information from huge data sets. But a closer look reveals that Big Data actually enhances the testing of hypothesis and experimentation, rather than replaces them.

Reductionism has largely influenced the development of science, culminating in its application to molecular biology. An increasing number of novel research findings have, however, shattered this view, showing how the molecular‐reductionist approach cannot entirely handle the complexity of biological systems. Within this framework, the advent of systems biology as a new and more integrative field of research is described, along with the form which has taken on the debate of reductionism versus holism. Such an issue occupies a central position in systems biology, and nonetheless it is not always clearly delineated. This partly occurs because different dimensions (ontological, epistemological, methodological) are involved, and yet the concerned ones often remain unspecified. Besides, within systems biology different streams can be distinguished depending on the degree of commitment to embrace genuine systemic principles. Some useful insights into the future development of this discipline might be gained from the tradition of complexity and self‐organization. This is especially true with regards the idea of self‐reference, which incorporated into the organizational scheme is able to generate autonomy as an emergent property of the biological whole. WIREs Syst Biol Med 2012. doi: 10.1002/wsbm.1181 This article is categorized under: Analytical and Computational Methods > Dynamical Methods Models of Systems Properties and Processes > Mechanistic Models