Significant advances in the cell biology of plant-microbe interactions have been achieved recently, to a large extent based on new technical approaches such as the use of fluorescent protein tags in model plants exploited in conjunction with available genetic resources. They have highlighted the pivotal role played by epidermal cells as the first site at which direct cell-to-cell contact takes place between the plant and microbes it may host. Here, we compare the cellular aspects of early biotrophic interactions with symbiotic and pathogenic microbes and evaluate the hypothesis that their hosting by plant cells share common traits related to the necessity of preserving host-cell integrity. The cellular events that accompany cell entry by the different biotrophs are divided into three categories, depending on whether the cellular changes are triggered by diffusible molecules, direct contact, or cell lumen penetration. Similarities and differences mirror the nutritional and developmental strategies of each plant-interacting organism, underlining the fact that plant cell entry represents a key aspect in the establishment of biotrophy.