The definitive axes of the mouse embryo can be unequivocally identified in embryos dissected at 5.5 days of gestation. However, how and when are these axes established remains an open question. At pre-implantation stages, different approaches have been aimed at determining if events occurring in the zygote influence the geometrical arrangement of the blastocyst. An intense debate has focused on whether the mouse embryo is a pre-patterned or a regulative structure. At post-implantation stages, the efforts have been concentrated in understanding how extra-embryonic tissues affect the formation of the primitive streak, the caudal marker of the anteroposterior axis. Here I summarize the last 10 years of research in this field.