The role of natural hybridization in the evolutionary history of numerous species is well recognized. The impact of introgressive hybridization and hybrid speciation has been documented especially in plant and animal assemblages. However, there remain certain areas of investigation for which natural hybridization and its consequences remain under-studied and under-appreciated. One such area involves the evolution of organisms that positively or negatively affect human populations. In this review, I highlight exemplars of how natural hybridization has contributed to the evolution of (i) domesticated plants and animals; (ii) pests; (iii) human disease vectors; and (iv) human pathogens. I focus on the effects from genetic exchange that may lead to the acquisition of novel phenotypes and thus increase the beneficial or detrimental (to human populations) aspects of the various taxa.