Plant parasitic nematodes are microscopic organisms that inhabit soil and plant tissues. Among such organisms, those of the genera Meloidogyne, Heterodera, Globodera, and Pratylenchus spp., are the most harmful, as they affect more than 2500 different species of plants, generating worldwide economic losses of over US$100 billion per year. These nematodes constitute a notable threat to the country’s progress and food security. Almost half of the global market for nematicides, which corresponds to US$ 1 billion per year, is used to control these nematodes. Non-fumigant nematicides are the most widely used in their control; however, many of them, such as carbamates and organophosphorus, are banned by environmental protection agencies because of their undesirable effects on non-target organisms. In the last 10 years, a new series of nematicides have emerged with different mechanisms of action than the old non-fumigant nematicides. Tioxazafen and fluazaindolizine are some of the latest new-generation nematicides that have come on the market. The rational design of new nematicides through in silico approaches combined with studies of the genetics and biochemistry of these microorganisms will help to better understand their management and control, aiming to reduce the environmental impact caused by the irrational use of nematicides.