Numerous studies carried out both in open field and laboratory scale have provided experimental evidence for a beneficial action of humic substances (HS) on plant growth and mineral nutrition. In fact, many products containing diverse concentrations of humic substances, mainly humic and fulvic acids, are marketed as plant growth enhancers all over the world. However, the incorporation of molecules containing humic substances into the granules of compound NPK fertilizers is not a common practice mainly due to technical difficulties and problems associated with the manufacture process of these mineral fertilizers. These problems are normally linked to the potential deleterious effects of granulation conditions (principally, heat and pH) on the structure and properties of molecules containing humic substances. In this review, we discuss several strategies for the incorporation of active molecules containing humic substances into granules of NPK compound fertilizers as well as the main constraints that have to be considered in this process, which normally depend on the agronomical results intended with the preparation of special humic-containing NPK compound fertilizers. We also discuss why, in our opinion, the beneficial action of HS in NPK compound fertilizers is more related to the "so called" indirect effects of HS on plant growth than to the "so called" direct effects.