The study of protein interactions is playing an ever increasing role in our attempts to understand cells and diseases on a system-wide level. This article reviews several experimental approaches that are currently being used to measure protein-protein, protein-DNA and gene-gene interactions. These techniques have now been scaled up to produce extensive genome-wide data sets that are providing us with a first glimpse of global interaction networks. Complementing these experimental approaches, several computational methodologies to predict protein interactions are also reviewed. Existing databases that serve as repositories for protein interaction information and how such databases are used to analyze high-throughput data from a pathway perspective is also addressed. Finally, current efforts to combine multiple data types to obtain more accurate and comprehensive models of protein interactions are discussed. It is clear that the evolution of these experimental and computational approaches is rapidly changing our view of biology, and promises to provide us with an unprecedented ability to model cells and organisms at a system-wide level.