Nucleation is the first stage in the formation of solid-state matter and its control constitutes a fundamental cornerstone for the tailored design and synthesis of functional materials. Understanding the chemistry at play in nucleation processes is far from straightforward, even for simple systems, and benefits from microscopic insights and principles scalable from clusters to crystallites with seminal bulk properties. Advances in the observation of molecular nucleation processes are intensively pursued to bridge the length and time scales involved. Typically, a recent study has captured images of the nucleation processes of the benchmark NaCl system. Similar experiments for the Metal-Organic Frameworks (MOFs) are extremely challenging due to the diversity of the pool of organic and metal-based species from which self-assembly occurs, and the many types of coordinative bonds and polymorphic structures. Different experimental studies can even lead to contradictory conclusions regarding the role of prenucleation and secondary building (SBUs) or growth units in the pathways of MOF assembly. The vast majority of the theoretical and computational research in the field of MOFs has been devoted to adsorption, diffusion and separa-tion processes, in a direct response to the urgent demand for applications of nanoporous materials, leaving less than a dozen works on nucleation. A direct consequence of the lack of knowledge in terms of MOF crystal growth is that most studies devoted to the development of synthesis routes of new MOFs are based on chemical intuition and trial and error procedures rather than on a rational analysis of the nucleation and crystal growth processes. It is in fact remarkable that while over 70,000 MOFs have been reported up to date, such little focus has been put on the stages of nucleation or crystallization. Therefore, it is often stated, not without despair, that each MOF family has to be considered as unique, despite the general commonalities in coordination chemistry that the members of this large family of materials share. The atomistic modeling of nucleation and crystal growth of MOFs faces several major challenges. The non-periodic structure models needed to model nucleation preclude the use of large scale, first-principle calculations at a reasonable cost, although advances in the field have been reported in recent years. Cost-effective classical force field simulations typically face the limitation of not being suitable in general to model bond breaking and formation, and of including a limited ensemble of structural motifs in the parameterization of the interatomic potentials. In consequence, force field-based calculations can lead to different conclusions depending on the choice of the interaction model, and thus suffer from lack of transferability. The selection of force field parameters, including atomic point charges, can be difficult in the continuously changing chemical environment in which nucleation takes place. The use of reactive force fields is regarded as a viable approach, as shown recently in a study of melting and recrystallization, but the accuracy of these methods requires substantial validation for both crystalline and pre-nucleating species, in order to ensure that the simulations are realistic. New avenues are expected from large-scale Monte Carlo (MC) and Molecular Dynamics (MD) simulations of MOFs with enhanced sampling techniques, following successes in modeling more straightforward systems. DFT based, ab-initio MD (AIMD) calculations, combining explicit solvent molecules and enhancing sampling techniques have also been employed to explore the competing mechanisms of formation of SBUs leading to MIL-101, MIL-53 and MOF-235. Morris 27 drew analogies between the nucleation and crystallization of MOFs and those of zeolites, leading to extensive research on the so-called Zeolitic Imidazolate Frameworks (ZIFs). However, the field is still in its infancy in terms of identifying the SBUs that drive the process of crystal growth. ZIF pre-nucleation building units with up to four metal atoms have been identified for ZIF-8, and CdIF-4, by mass spectrometry techniques. Atomic Force Microscopy (AFM) was also employed for CdIF-4, and it was the first time that metal-ligand species relevant for the surface nucleation and growth in a MOF were identified. The evolution of metal-organic aggregates of one or only a few Zn atoms and intermediate species, up to bulkier cluster units of ∼ 2 nm has also been evidenced in the formation of ZIF-8 from mass spectrometry and X-ray scattering and diffraction. However, the structure of the larger units could not be correlated with those appearing in ZIF-8 and thus they were assigned to be amorphous precursors. In a remarkable attempt to lay out a systematic framework of MOF growth, a recent investigation by Filez et al. has combined a variety of experimental methods and computations to link the prenucleation, nucleation and crystallization regimes in Co ZIF-67, by discriminating those metal-organic complexes involved in initiating nucleation and the species required for oligomerization into extended MOF networks. A complex framework of non-classic multi-stage nucleation routes is laid out in that investigation, which is expected to be largely driven by the rich metal-linker reaction chemistries concurring in the amalgam of species in the synthesis of this MOF. Very recently, Balestra and Semino 25 have studied the self-assembly of ZIF-8 via a force field that includes the possibility of breaking and forming metal-ligand bonds to achieve molecular details of the nucleation of ZIF-8.