The genomes of mammals and birds show dramatic variation in base composition over large scales, the so called isochore structure of the genome. The origin of isochores is still controversial: various neutral and selectionist models have been proposed – and criticized – since the discovery of isochores in the 1970s. The availability of complete mammalian genomes has yielded new opportunities for addressing this question. In particular, it was recently proposed that (i) the isochore structure is declining in many mammalian groups, and that (ii) GC-content is influenced by local recombination rate, possibly via the mechanism of GC-biased gene conversion. In this article we review the existing support for these two hypotheses, and discuss how they can be combined to provide a new perspective on isochore evolution.