Host-specialized pathogens are credited with the maintenance of tropical forest diversity under the Janzen-Connell hypothesis. Yet, in diverse forests, selection may favor pathogens with broad host ranges, given their passive dispersal and the relative rarity of tree species. We surveyed the host associations of potential pathogens isolated from symptomatic seedlings in forests in Panama and used inoculations to assess the pathogenicity and host ranges of 27 fungal isolates, and differences among tree species in susceptibility. Thirty-one of the 33 nonsingleton operational taxonomic units (OTUs) isolated from seedlings are multi-host. All 31 multi-host OTUs exhibit low to moderate specialization, and we observed phylogenetically overdispersed host use for 19 OTUs. The pathogenicity of 10 isolates was experimentally confirmed; nine caused disease in seedlings in multiple families. However, the outcome of infection differs among tree species susceptible to a given multi-host pathogen. Furthermore, some tree species were seemingly resistant to all fungi tested, while others were susceptible to multiple fungi. Tree species adapted to environments with lower disease pressure were most likely to exhibit disease. Our results suggest that generalist pathogens contribute to the maintenance of local and regional forest diversity via host-specific impacts and the exclusion of disease-sensitive trees from disease-prone habitats.