For several years we have been concentrating on developing methods for large-scale sequencing projects and the resulting software is used in many major laboratories and genome centers. In the course of this work we devised a very powerful graphical user interface for use in our sequence assembly and editing program GAP4 (1), and recently we have started to write replacements for our old analysis programs NIP (2) and SIP (3), and these entirely new programs have the same user interface as GAP4. The older programs were described in the previous edition of this book (4), and are largely unchanged, but are still included in our package distribution. Here we give an overview of our methods for sequencing projects and also of our new analytical programs, all of which are fully documented in our 500-page manual which is available for printing or as an HTML document ( http://www.mrc-lmb.cam.ac.uk/pubseq ). This site also contains color versions of the figures used in this chapter and information about obtaining our package.