Recent studies of Drosophila and humans indicate that aberrant genetic recombination is an important component of nondisjunction in both species. In both, a proportion of nondisjunction is associated with failure to pair and/or recombine and in both, exchanges which are either too distal or too proximal increase the likelihood of malsegregation. In this review we provide two perspectives on these observations: first, a review of exchange and chromosome segregation in model organisms, focusing on Drosophila, and secondly an overview of nondisjunction in humans. This format allows us to describe the paradigms developed from studies of model organisms and to ask whether these paradigms apply to the human situation.