This review of naturally occurring phytochemicals with biological activity against plant-parasitic nematodes focuses on several diverse classes of compounds, including polythienyls, alkaloids, phenolics, polyacetylenes, fatty acids, terpenoids, and others. The nematotoxic mode of action and physiological role of most of these compounds in plants are unknown, although some are synthesized in response to nematode infection. Only a few plant families, primarily the Asteraceae and Fabaceae, have been examined for existence of nematotoxic substances. In a few cases, synthetic analogs of naturally occurring compounds have been synthesized and have possessed stronger biological activity than the naturally occurring ones. Enhanced research and development of phytochemical nematicides and analogs could provide safe, selective compounds for minimizing the multibillion dollar annual losses inflicted by phytoparasitic nematodes in the U.S.