There is no doubt that Trichoderma is an inhabitant of the rhizosphere that plays an important role in how plants interact with the environment. Beyond the production of cell wall degrading enzymes and metabolites, Trichoderma spp. can protect plants by inducing faster and stronger immune responses, a mechanism known as priming, which involves enhanced accumulation of dormant cellular proteins that function in intracellular signal amplification. One example of these proteins is the mitogen-activated protein kinases (MAPK) that are triggered by the rise of cytosolic calcium levels and cellular redox changes following a stressful challenge. Transcription factors such as WRKYs, MYBs, and MYCs, play important roles in priming as they act as regulatory nodes in the transcriptional network of systemic defence after stress recognition. In terms of long-lasting priming, Trichoderma spp. may be involved in plants epigenetic regulation through histone modifications and replacements, DNA (hypo)methylation, and RNA-directed DNA methylation (RdDM). Inheritance of these epigenetic marks for enhanced resistance and growth promotion, without compromising the level of resistance of the plant’s offspring to abiotic or biotic stresses, seems to be an interesting path to be fully explored.