Paecilomyces spp. and Byssochlamys spp. are heat-resistant fungi important to industry because they can cause food and beverage spoilage, incurring economic loss. The consequences of food or beverage fungal colonization is the loss of nutritional value, structure and taste, and the possibility of producing toxic secondary metabolites that may result in medical problems. Furthermore, these fungi can infect animals and humans and it is unknown if contaminated foods may be fomites. P. variotii is the principal agent of food spoilage or contamination and it is most frequently associated with human hyalohyphomycosis with clinical manifestations including peritonitis, cutaneous and disseminated infections, among others. Byssochlamys spp. had not been identified as a cause of systemic infection until the case of a dog with a fungal infection, after immunosuppressive therapy. P. variotii has clinical importance because it causes severe infection in immunosuppressed patients and also because the number of immunocompetent infected patients is increasing. This review draws attention to the ability of these species to grow at high temperatures, to colonize food products, and to cause human disease.