Protein-protein interactions are the building blocks of cellular networks and at the heart of cellular regulation. However, their experimental identification is still a challenge. This chapter is concerned with the determination of protein-protein interactions by bioinformatical methods. These often can operate just on sequence information. Further required information is derived from public knowledge in literature databanks and biochemical databases as well as from the sequences themselves and iterative sequence comparisons. Further tools include domain analysis, structure prediction, and genome context methods. The results are predicted binary interactions and complete interaction networks.