Many necrotrophic plant pathogenic fungi belonging to the class of Dothideomycetes produce phytotoxic metabolites and peptides that are usually required for pathogenicity. Phytotoxins that affect a broad range of plant species are known as non-host-specific toxins (non-HSTs), whereas HSTs affect only a particular plant species or more often genotypes of that species. For pathogens producing HSTs, pathogenicity and host specificity are largely defined by the ability to produce the toxin, while plant susceptibility is dependent on the presence of the toxin target. Non-HSTs are not the main determinants of pathogenicity but contribute to virulence of the producing pathogen. Dothideomycetes are remarkable for the production of toxins, particularly HSTs because they are the only fungal species known so far to produce them. The synthesis, regulation, and mechanisms of action of the most important HSTs and non-HSTs will be discussed. Studies on the mode of action of HSTs have highlighted the induction of programed cell death (PCD) as an important mechanism. We discuss HST-induced PCD and the plant hypersensitive response upon recognition of avirulence factors that share common pathways. In this respect, although nucleotide-binding-site-leucine-rich repeat types of resistance proteins mediate resistance against biotrophs, they can also contribute to susceptibility toward necrotrophs.