The tectonosedimentary development of the South Atlantic is compared with the Central Atlantic margins, which are associated with major episodes of magmatism during the Mesozoic continental break-up. Subsequently, the Cenozoic break-up in the North Atlantic led to the formation of the volcanic Norwegian-Greenland conjugate margins. The DSDP boreholes in the magma-poor Iberian-Newfoundland margins have confirmed the occurrence of exhumed mantle at the ocean-continent transition. This possibility has been suggested for the South Atlantic margins, but still lacks confirmation from drilling. The Red Sea and the Gulf of Aden may be considered as natural laboratories to study the break-up processes and formation of divergent continental margins. Using key geological and geophysical data, we compare some of the structures observed in incipient stages of basin formation between the African and the Arabian plates with the structures observed in older sedimentary basins associated with the Gondwana break-up. We also analyse deep seismic reflection profiles and potential field data at the continent-ocean boundary of these conjugate margins, using palinspastic reconstructions to define the corresponding seismic pairs. We conclude that the Red Sea and the Gulf of Aden display remarkable differences to the Iberian-Newfoundland margins, and notable similarities with the South Atlantic margins.