The success of structural genomics initiatives requires the development and application of tools for structure analysis, prediction, and annotation. In this paper we review recent developments in these areas; specifically structure alignment, the detection of remote homologs and analogs, homology modeling and the use of structures to predict function. We also discuss various rationales for structural genomics initiatives. These include the structure-based clustering of sequence space and genome-wide function assignment. It is also argued that structural genomics can be integrated into more traditional biological research if specific biological questions are included in target selection strategies.