Probiotics are live, nonpathogenic microorganisms that confer benefits to human health when administered in adequate amounts. Among the frequent proposed health benefits attributed to probiotics, their ability to interact with the host immune system is now well demonstrated. Although history has revealed that probiotics were part of fermented foods in the past, clinicians have started to use them therapeutically in regular diets. Moreover, the use of genetically modified probiotics to deliver molecules of therapeutic interest is gaining importance as an extension of the probiotic concept. This chapter summarizes some of the recent findings and perspectives on the use of both traditional and genetically modified probiotics to treat human diseases as well as what the future may hold concerning the use of these probiotics in humans.