Human and plant pathogenic fungi have a major impact on public health and agriculture. Although these fungi infect very diverse hosts and are often highly adapted to specific host niches, they share surprisingly similar mechanisms that mediate immune evasion, modulation of distinct host targets, and exploitation of host nutrients, highlighting that successful strategies have evolved independently among diverse fungal pathogens. These attributes are facilitated by an arsenal of fungal factors. However, not a single molecule, but rather the combined effects of several factors enable these pathogens to establish infection. In this review we discuss the principles of human and plant fungal pathogenicity mechanisms and discuss recent discoveries made in this field. This article is protected by copyright. All rights reserved.