Aneuploidy is a crucial issue in human reproductive biology, accounting for both a significant proportion of miscarriages and, among liveborns, multiple congenital malformation syndromes such as Down Syndrome. Although the etiology of human aneuploidy remains poorly understood, recent studies have elucidated certain fundamental correlates of meiotic nondisjunction, such as altered recombination. These features are extraordinarily similar to those associated with chromosome misbehavior in Drosophila melanogaster females. Furthermore, these organisms also share a significant level of achiasmate chromosome nondisjunction. Here we describe in detail the processes of achiasmate chromosome segregation in Drosophila and discuss how they may be most effectively applied to our understanding of the etiology of human aneuploidy. In particular, we examine the possibility that similar “backup” mechanisms of chromosome segregation might function in mammalian meiosis, particularly mammalian females. Drawing upon observations made in flies, we also propose a new model for the segregation of achiasmate chromosomes in humans.