Abstract: The recent explosion of high throughput experimental technologies for characterizing protein interactions has generated large amounts of data describing interactions between thousands of proteins and producing genome scale views of protein assemblies. The systems-level views afforded by these data hold great promise of leading to new knowledge, but also involve many challenges. Deriving meaningful biological conclusions from these views crucially depends on our understanding of the approximation and biases that enter into deriving and interpreting the data. The challenges and rewards of interaction proteomics are reviewed here using as an example the latest comprehensive high throughput analyses of protein interactions in yeast.