During the last two decades, a systematic re-examination of the whole information science field has taken place around the FIS—Foundations of Information Science—initiative. With the occasion of its Fourth Conference in Beijing 2010, a group of selected contributors and leading practitioners of those fields have been invited to contribute to this Special Issue. What is the status of information science today? What is the relationship between information and the laws of nature? Is information merely “physical”? What is the difference between information and computation? Has the genomic revolution changed the contemporary views on information and life? And what about the nature of social information? Cogent answers to these questions and to quite many others are attempted in the contributions that follow.