The genome of monotremes, like the animals themselves, is unique and strange. The importance of monotremes to genomics depends on their position as the earliest offshoot of the mammalian lineage. Although there has been controversy in the literature over the phylogenetic position of monotremes, this traditional interpretation is now confirmed by recent sequence comparisons. Characterizing the monotreme genome will therefore be important for studying the evolution and organization of the mammalian genome, and the proposal to sequence the platypus genome has been received enthusiastically by the genomics community. Recent investigations of X-chromosome inactivation, genomic imprinting and sex chromosome evolution provide good examples of the power of the monotreme genome to inform us about mammalian genome organization and evolution.