Synthetic Biology approaches are proposing model systems and providing experimental evidences that life can arise as spontaneous chemical self-assembly process where the ability to reproduce itself is an essential feature of the living system. The appearance of early cells has required an amphiphilic membrane compartment to confine molecular information against diffusion, and the ability to self-replicate the boundary layer and the genetic information. The initial spontaneous self-replication mechanisms based on thermodynamic instability would have evolved in a prebiotic and later biological catalysis. Early studies demonstrate that fatty acids spontaneously assemble into bilayer membranes, building vesicles able to grow by incorporation of free lipid molecules and divide. Early replication mechanisms may have seen inorganic molecules playing a role as the first catalysts. The emergence of a short ribozyme or short catalytic peptide may have initiated the first prebiotic membrane lipid synthesis required for vesicle growth. The evolution of early catalysts towards the simplest translation machine to deliver proteins from RNA sequences was likely to give early birth to one single enzyme controlling protocell membrane division. The cell replication process assisted by complex enzymes for lipid synthesis is the result of evolved pathways in early cells. Evolution from organic molecules to protocells and early cells, thus from chemistry to biology, may have occurred in and out of the boundary layer. Here we review recent experimental work describing membrane and vesicle division mechanisms based on chemico-physical spontaneous processes, inorganic early catalysis and enzyme based mechanisms controlling early protocell division and finally the feedback from minimal genome studies.