Phytopathogenic fungi (PPF) are an important group of organisms that regulate populations of wild plants and reduce crop yields, the quality of feed and food during storage. PPF with necro- and hemibiotrophic lifestyles are capable of producing secondary metabolites of various chemical structure with a wide range of biological activity. These substances, along with protein effectors, may be used by fungi to colonize plant substrates, as well as to compete with phytophagous arthropods and phytopathogenic microorganisms (fungi, bacteria, and viruses), to survive in soil, seeds, and on plant residues, countering saprotrophs and antagonists. The chapter discusses chemical ecology of PPF and main approaches to elucidate the ecological role of secondary metabolites produced by them. They were found mainly to be multifunctional molecules exhibiting a wide range of biological activity. However, phytotoxicity and cytotoxicity are their most common properties. It would be extremely interesting to understand further what this is related to, not only from the point of view of chemical ecology but also the coevolution of fungi with other organisms. Some PPF phytotoxins demonstrate high potential for the development of herbicides and anticancer drugs. However, chemical modification may need to increase the efficacy and selectivity.