This paper presents CoScribe, a concept and prototype system for the combined work with printed and digital documents, which supports a large variety of knowledge work settings. It integrates novel pen-and-paper-based interaction techniques that enable users to collaboratively annotate, link and tag both printed and digital documents. CoScribe provides for a very seamless integration of paper with the digital world, as the same digital pen and the same interactions can be used on paper and displays. As our second contribution, we present empirical results of three field studies on learning at universities. These motivated the design of CoScribe and were abstracted to a generic framework for the design of intuitive pen-and-paper user interfaces. The resulting interaction design comprising collaboration support and multiuser visualizations has been implemented and evaluated in user studies. The results indicate that CoScribe imposes only minimal overhead on traditional annotation processes and provides for a more efficient structuring and retrieval of documents.