This perspective begins with the discovery of the Grignard reaction by a graduate student in the last years of the 19th century, followed by describing why it has remained largely unexplained for more than a century. From the summary of what has been achieved, focusing on the computational aspects, it is now clear that further studies of the chemistry of any chemical species that is highly sensitive to solvents, such as Group I and II elements, require a holistic approach that includes the solute and the solvent together. <i>Ab initio</i> molecular dynamics, which meets these requirements, has produced some results but has hit hard limits due to its relatively high computational costs. In these days, it is becoming clear that data-driven methods, including machine learning potentials and simulations driven by quantitative on-the-fly calculation of relevant observables, have the potential to better and more completely explore the very large chemical space associated with the presence of a large number of species in solution. These methodologies have the chance to give the keys to enter the challenging and still poorly explored world of chemical species whose behaviour and reactivity are strongly influenced by the solvent and the experimental conditions. 30–33 This proposition rationalized the formation of organic products that could not originate from a Grignard addition of R − to the carbonyl, such as the dimer via the C–C bond of the two carbonyl substrates. Recent experiments fully clarified this dichotomy. Thus, Woerpel et al. established that the addition to aliphatic ketones does not favour single electron transfer and prefers the nucleophilic addition pathway. 34 The SET reaction can occur with conjugated ketones but is not the exclusive pathway. In the case of phenyl ketone, the SET pathway was dominant only with tertiary alkyl like tert -butyl as the R group in RMgX. The dinuclear magnesium complex and two molecules of substrate were considered as the starting point to include the 1 : 1 stoichiometry between the substrate (formaldehyde) and Grignard reagent (CH 3 MgCl). The reaction mechanism was then studied in the gas phase and with dimethyl ether as solvent. It was shown that the formaldehyde coordinated to a single magnesium reacts preferentially with the methyl group of the other magnesium to form a dichloride-ethoxide-bridged species. This dinuclear species could undergo a further Grignard reaction with the remaining formaldehyde and methyl groups. The complete pathway is shown in Fig. 3b . The energy barriers of these reactions were found to be low, with the first reaction having a lower energy barrier than the second one. It was also found that the coordinating solvent (one Me 2 O per magnesium) did not change the global features, nor did the replacement of Cl by Br. Fig. 3 (a) Suggested non-computed 6-membered ring transition state for the Grignard reaction. (b) Reaction mechanism identified by DFT(B3LYP) calculations with CH 3 MgCl and formaldehyde (no solvent) as models. Figure adapted from ref. 37 . The authors also investigated the SET mechanism. 7 List of monomers and dimers considered as reagents and associated free energy of activation in kcal mol −1 , as determined by thermodynamic integration. Adapted from ref. 96 , under CC-BY-NC-ND 4.0 license. The activation energy for the addition of the methyl group to the acetaldehyde carbon to form a magnesium-bound isopropyl alkoxide ligand was determined for each of these species. All five geminal reactions induce a four-centre transition state (C Created by potrace 1.16, written by Peter Selinger 2001-2019 ]]> O–Mg–C Me ) which creates an electronic vacancy at the Mg centre associated with the cleavage of the Mg–methyl bond. 8 Comparison of the reaction mechanisms for monomeric (B gem ) and dimeric (F vic ) complexes. In the first case, the reaction is helped by an incoming solvent molecules coordinating Mg at the TS. In the second case, the initial higher coordination of the metal centres allows reaching the TS without any major reorganisation of the environment. Figure adapted from ref. 96 , under CC-BY-NC-ND 4.0 license. The vicinal reactions also occur via a four-centre type transition state, obtained by translocation of the carbonyl group from a peripheral to a bridging position. However, the solvent contribution is different from that in the geminal reactions. 6.1.2 Structural features of the transition states in the geminal and vicinal pathways In the 1970s, crystal structures were used to determine the geometrical features of the nucleophilic addition to a carbonyl group. 97 The examination of the crystal structure data was completed with ab initio Hartree–Fock calculations using H − as the nucleophile and H 2 CO as the substrate, all in the gas phase due to the notorious computational limitations of the time. 98 Both studies showed that the nucleophile, Nu, approaches the carbonyl carbon with a Nu⋯C–O angle larger than 90° (angle between 105 and 110°, known as the Bürgi–Dunitz angle). These results are in agreement with the experiments. As mentioned in the introduction, experimental data have established that alkyl ketones do not go via the SET mechanism and prefer the nucleophilic pathway and that often the nucleophilic and SET pathways are both possible even with conjugated carbonyl species. 34,35 Fig. 9 Spin density localization on (a) ˙ Mg(Cl)(acetaldehyde)(THF) 2 and (b) ˙ Mg(Cl)(fluorenone)(THF) 2 . Adapted from ref. 96 , under CC-BY-NC-ND 4.0 license. In our opinion, the most important message emerging from these calculations is the identification of a manifold of accessible pathways for the Grignard reaction. Many magnesium complexes are competent for a diversity of nucleophilic mechanisms. Furthermore, in the case of conjugated carbonyl substrates, the nucleophilic and SET pathways can also have similar activation barriers. The nature of the Grignard reagent, substrate and solvent also