Various genetic events during the process of natural evolution shape the landscape of the genomes. In this chapter, we explore an approach to investigating multiple genomes in order to unravel their complex relationships that go beyond their placement on a phylogeny. To this end, we treat genes as the smallest syntactic unit on the genome and explore their relative organization across multiple genomes. In the first half of the chapter, we discuss mathematical models to capture the combinatorial structures of this relative organization and statistical models to study their distributions. In the second half of the chapter, we apply these models to analyze the relationship between three closely related plant genomes.