Plant-parasitic nematodes are estimated to cause global annual losses of more than US$ 100 billion. The number of registered nematicides has declined substantially over the last 25 years due to concerns about their non-specific mechanisms of action and hence their potential toxicity and likelihood to cause environmental damage. Environmentally beneficial and inexpensive alternatives to chemicals, which do not affect vertebrates, crops, and other non-target organisms, are therefore urgently required. Nematophagous fungi are natural antagonists of nematode parasites, and these offer an ecophysiological source of novel biocontrol strategies. In this first section of a two-part review article, we discuss 83 nematicidal and non-nematicidal primary and secondary metabolites found in nematophagous ascomycetes. Some of these substances exhibit nematicidal activities, namely oligosporon, 4',5'-dihydrooligosporon, talathermophilins A and B, phomalactone, aurovertins D and F, paeciloxazine, a pyridine carboxylic acid derivative, and leucinostatins. Blumenol A acts as a nematode attractant. Other substances, such as arthrosporols and paganins, play a decisive role in the life cycle of the producers, regulating the formation of reproductive or trapping organs. We conclude by considering the potential applications of these beneficial organisms in plant protection strategies.