For nearly a century, the Fischer-Tropsch (FT) reaction has been subject of intense debate. Various molecular views on the active sites and on the reaction mechanism have been presented for both Co- and Fe-based FT reactions. In the last 15 years, the emergence of a surface-science- and molecular-modeling-based bottom-up approach has brought this molecular picture a step closer. Theoretical models provided a structural picture of the Co catalyst particles. Recent surface science experiments and density functional theory (DFT) calculations highlighted the importance of realistic surface coverages, which can induce surface reconstruction and impact the stability of reaction intermediates. For Co-based FTS, detailed microkinetic simulations and mechanistic experiments are moving toward a consensus about the active sites and the reaction mechanism. The dynamic phase evolution of Fe-based catalysts under the reaction conditions complicates identification of the surface structure and the active sites. New techniques can help tackle the combinatorial complexity in these systems. Experimental and DFT studies have addressed the mechanism for Fe-based catalysts; the absence of a clear molecular picture of the active sites, however, limits the development of a molecular view of the mechanism. Finally, direct CO2 hydrogenation to long-chain hydrocarbons could present a sustainable pathway for FT synthesis.