In mutualism, reciprocal altruism requires feedback and a means for directing benefits to cooperators. Experiments with cross-feeding microbial species provide examples of how differences in the cost of cooperation influence interactions that lead to improved mutualisms. After Desulfovibrio vulgaris and Methanococcus maripaludis are cocultured, samples of either co-adapted species can improve yields relative to samples from the ancestral coculture. Escherichia coli and Salmonella enterica serovar Typhimurium can rapidly evolve cross-feeding interactions, including secretion of metabolically costly compounds from cells of the latter species. Studying mutualisms in microbes could enhance our ability to engineer novel consortia and will improve our understanding of complex feedbacks between genetic variation and community ecology.