The formation of the blastocyst during preimplantation development constitutes a unique opportunity to study living mammalian embryos. The blastocyst consists of a surface epithelium enveloping a fluid-filled lumen and a cluster of pluripotent stem cells. This specific architecture is key to further the development of the mammalian embryo. Using biophysical measurements and modelling, we have uncovered some of the mechanisms shaping the blastocyst, such as the compaction of the embryo and differential positioning of cells within the embryo. Here, we will describe how the mechanical properties of cells and osmotic flows can control the formation and the positioning of the first mammalian lumen.