The fabrication of polyelectrolyte multilayer films (PEMs) using the Layer-by-Layer (LbL) method is one of the most versatile approaches for manufacturing functional surfaces. This is the result of the possibility to control the assembly process of the LbL films almost at will, by changing the nature of the assembled materials (building blocks), the assembly conditions (pH, ionic strength, temperature, etc.) or even by changing some other operational parameters which may impact in the structure and physico-chemical properties of the obtained multi-layered films. Therefore, the understanding of the impact of the above mentioned parameters on the assembly process of LbL materials plays a critical role in the potential use of the LbL method for the fabrication of new functional materials with technological interest. This review tries to provide a broad physico-chemical perspective to the study of the fabrication process of PEMs by the LbL method, which allows one to take advantage of the many possibilities offered for this approach on the fabrication of new functional nanomaterials. Display omitted •Layer-by-layer (LbL) method is a powerful tool for the assembly of supramolecular materials.•Absence of any theoretical limitations to the assembled compounds and the geometry of the final material•Assembly of LbL multilayers is governed by an intricate balance of interactions.•Study of physico-chemical properties and structure of the LbL films is critical for their potential applications.