Marsupials and monotremes are 'alternative mammals', independent experiments of mammalian evolution that diverged from placental mammals 180 and 210 million years ago (MYA), respectively. Marsupials (e.g. kangaroo, opossum) and monotremes (e.g. platypus) differ from placental mammals in many characteristics, particularly reproduction. With their early divergence from placentals, they fill the phylogenetic gap between the mammal-reptile divergence 310 MYA and the placental radiation 100 MYA. Their genomes are similar in size to those of placentals, but their chromosomes are quite distinctive. Marsupials have a few very large and very conserved chromosomes, while monotremes show a reptile-like size dichotomy and have a unique chain of ten sex chromosomes. Studies of gene arrangement in marsupials and monotremes have delivered many surprises that necessitate re-evaluation of the function and control of several genes in all mammals including humans, and provide new insights into the evolution of the mammalian genome, particularly the sex chromosomes. With the imminent sequencing of the genomes of two marsupials (the short-tailed grey Brazilian opossum and an Australian model kangaroo) and the platypus, much more detailed comparisons become possible. Even the first few analyses of marsupial and platypus sequences confirm the value of sequence comparisons for finding new genes and regulatory regions and exploring their function, as well as deducing how they evolved.