Tolerance, defined as the reduction in the damage that pathogen infection causes in hosts, is a defense mechanism as widespread in plants as resistance, but much less studied. Advances in the knowledge of tolerance have been hampered by the difficulty to distinguish in experimental settings this defense from quantitative resistance, which are often confounded. In this review, Israel Pagán y Fernando García-Arenal highlight the conceptual unity underlying the different formulations of tolerance proposed over the past century. They also discuss the abundant evidence supporting that this defense strategy is widespread in plants, and plays a key role in the epidemiology and ecology, evolution and co-evolution of plants and pathogens. Lastly, the more limited understanding on the genetic determinants and molecular mechanisms of tolerance are summarized. This work provides a unified conceptual framework that facilitates studies of this key plant defense, and its application to control crop diseases.