The availability of an increasing number of whole genome sequences presents us with the need for tools to quickly put them into a nucleotide-level multiple alignment. Mercator and MAVID are two programs that can be combined to accomplish this task. Given multiple whole genomes as input, Mercator is first used to construct an orthology map, which is then used to guide nucleotide-level multiple alignments produced by MAVID. These programs are both fast and freely available, allowing researchers to perform genome alignments on a single laptop. This tutorial will guide the researcher through the steps required for whole-genome alignment with Mercator and MAVID.