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This book provides the application of response surface methodology in modeling and optimizing culture conditions of milk kefir grains for nutrition and health. The operational conditions considered during the growth of the kefir grains were number of rotations, fat content and time. This led to an increase in biomass of kefir grains with high level of probiotics. In order to obtain the optimum growth of kefir grains; culture conditions, culture liquid and presence of random effects were considered. Thus, an experiment was carried out in order to obtain the data which was used to establish the necessary conditions on the growth of kefir grains. Box-Behnken design was used to model the data and hence identify optimal levels of conditions for growing kefir grains. Further the random effects were identified. The evaluation of the presence of random effects on growth of kefir grains was established. The Design expert was used to extract data through controlled experiment.