Entomopathogenic nematodes (EPNs) are insect-parasitic nematodes that rapidly kill insects and have been used for biocontrol of insect pests. The symbiotic bacteria that these EPNs carry have traditionally been thought to be the only source of virulence, however, we have shown substantial proof that these nematodes do actively contribute to killing the insect-host. We show that EPNs from the genus Steinernema release excreted-secreted proteins (ESPs) at the early stages of infecting a host and these ESPs are toxic to insects. This paradigm shift in the EPN field merited further exploration into the mechanisms of toxicity of the nematode derived ESPs. Profiling of the ESPs revealed a complex mixture of proteins predicted to be involved in tissue damage and host immune modulation. Many of these proteins were also found to be highly similar to proteins used by vertebrate parasites. We found a core suite of proteins utilized by two Steinernema species of EPNs at the early stages of infection indicating these proteins have a central and important role in insect-parasitology and potentially vertebrate-parasitology as well. We continue to identify candidate active proteins in the ESPs of Steinernema feltiae and produce these proteins for characterization.