Trichoderma harzianum strain T22 is an effective biological control strain produced by protoplast fusion with the goal of obtaining highly rhizosphere competent biocontrol fungi. This strain is able to colonize all parts of the plant root system and to modulate the composition of the rhizosphere microbiome. Interestingly, these abilities are not particularly affected by soil type, plant species nor by geographical zone. The root colonization by T. harzianum T22 and consequent plant-microbe interactions can be profound in terms of plant disease control, growth and productivity. The biocontrol activity of T. harzianum T22 has been reported against several plant pathogenic fungi such as F. graminearum, R. solani, Pythium ultimum, and Sclerotium rolfsii. The mechanisms by which T. harzianum acts are multiple and include mycoparasitism, antibiosis, competition for nutrients and/or space, tolerance to stress through enhanced root and plant development, induced resistance, solubilization and sequestration of inorganic nutrients and inactivation of the pathogen’s enzymes. The beneficial features of Trichoderma harzianum T22 make it a successful component of many biological products used for agriculture worldwide.