Microbes are sources of a diverse array of phytotoxic compounds. These compounds are generally structurally different from commercial herbicides, targeting different molecular sites of action within the plant. These novel structures and sites can be excellent leads for the discovery and development of safer synthetic herbicides. Microbial phytotoxins are often more environmentally benign than synthetic herbicides. Examples of phytotoxins from fungi (AAL‐toxin, cornexistin, cyperin, and tentoxin) with novel structures and sites of action are discussed. AAL‐toxin is toxic to a wide variety of weeds at very low dose rates. AAL‐toxin and many of its analogues kill plants by inhibiting a ceramide synthase‐like enzyme, causing rapid accumulation of free sphingoid bases that disrupt membranes. Cornexistin appears to be metabolically cnverted to an inhibitor of certain aspartate amino transferase isoenzymes. Its activity can be reversed by feeding aspartate and glutamate or with tricarboxylic acid cycle intermediates. Its activity is much like that of (aminooxy)acetate. Cyperin is a diphenylether phytotoxin that inhibits protoporphyrinogen oxidase, but does not kill plants by this mechanism. It appears to have other effects on porphyrin metabolism. Tentoxin is toxic by two mechanisms. It disrupts chloroplast development by inhibiting the processing of a nuclear‐coded plastid protein, and it also inhibits photophosphorylation by acting as an energy transfer inhibitor of coupling factor 1 ATPase. Other examples of phytotoxins from microbes with promise as herbicides will be mentioned.