Evolutionary conservation of homologous gene products from distantly related organisms provides an information resource of great value for elucidating protein structure and function. Sequence similarities also serve as molecular cross-references between diverse organisms that offer different, or complementary, experimental approaches for analyzing gene expression and biochemistry in normal and abnormal states. There are now countless examples of information about a protein from one species contributing to the understanding of biological phenomena or disease in another species. Such connections are often unanticipated and surprising, but there is an opportunity to make them more systematically as concerted genome sequencing projects progress. In the present review we focus on connections between yeast and human proteins and their functional implications. We present several 'case studies' as well as survey results derived from comprehensive sequence comparisons among all yeast and human proteins currently present in the public databases.