Every new scientific discipline or methodology reaches a point in its maturation where it is fruitful for it to turn its gaze inward, as well as backward. Such introspection helps to clarify the essential structure of a field of study, facilitating communication, pedagogy, standardization, and the like, while retrospection aids this process by accounting for its beginnings and underpinnings. In this spirit, PLoS Computational Biology is launching a new series of themed articles tracing the roots of bioinformatics. Essays from prominent workers in the field will relate how selected scientific, technological, economic, and even cultural threads came to influence the development of the field we know today. These are not intended to be review articles, nor personal reminiscences, but rather narratives from individual perspectives about the origins and foundations of bioinformatics, and are expected to provide both historical and technical insights. Ideally, these articles will offer an archival record of the field's development, as well as a human face on an important segment of science, for the benefit of current and future workers. Upcoming articles, already commissioned, will cover the roots of bioinformatics in structural biology, in evolutionary biology, and in artificial intelligence, with more in the works. These topics are obviously very broad, and so are likely to be subdivided or otherwise revisited in future installments by authors with varying perspectives. Topics and authors will be chosen at the discretion of the editors along lines broadly corresponding to the usual content of this journal. The author, having been asked to serve as Series Editor by the Editor-in-Chief, will endeavor to maintain a uniform flow of articles solicited from luminaries in the field. As a starting point to the series, I offer below a few vignettes and reflections on some longer-term influences that have shaped the discipline. I first consider the unique status of bioinformatics vis-a-vis science and technology, and then explore historical trends in biology and related fields that anticipated and prepared the way for bioinformatics. Examining the context of key moments when computers were first taken up by early adopters reveals how deep the roots of bioinformatics go.