This review explores the abilities of beneficial microbes including probiotics to stimulate mucosal and systemic immunity, so that global vaccination strategies may be enhanced. Beneficial microbes secrete microbial factors and express cell surface features that stimulate different types of immune cells to alter their gene expression programs and produce different sets of cytokines and immune mediators. Microbes can affect the B lymphocyte program, and the production of different antibody subclasses due to class switching. Immune responses to antigenic challenges as a result of vaccination may be stimulated by B lymphocyte-promoting signals that result from microbial stimulation. Effector and regulatory T lymphocyte programs may be modulated by microbial effects on different signalling pathways. Beyond adaptive immunity, beneficial microbes may stimulate signalling pathways in intestinal epithelial cells, macrophages, and dendritic cells of the innate immune system. Beneficial microbes including probiotics may "prime" the immune system and supplement nutritional approaches so that infants and young children in the developing world are vaccine-ready. If these strategies can be combined, success rates for diverse vaccines may effectively increase in resource-poor regions of the world.