Many tasks in computational biology are dependent on the existence of reference genomes. If you are performing a sequence alignment, finding genes, or studying genetics of populations at several points of your work, you will be directly or indirectly using a genome reference. In this chapter, we will develop some recipes to work with reference genomes and deal with varying quality of references (which can vary for high-quality, like with the human genome, to problematic with non-model species). We will also see how to deal with genome annotations (working with text databases that will point us to interesting features in the genome) and extract sequence data using the annotation information. Also, we will try to find some gene orthologues across species. Finally, we will access a gene ontology (GO) database.