The gut microbiota interact with innate immune cells and play an important role in shaping the immune system. Many factors may influence the composition of the microbiota such as mode of birth, diet, infections and medication including antibiotics. In diseases with a multifactorial etiology, like type 1 diabetes, manipulation and alterations of the microbiota in animal models have been shown to influence the incidence and onset of disease. The microbiota are an important part of the internal environment and understanding how these bacteria interact with the innate immune cells to generate immune tolerance may open up opportunities for development of new therapeutic strategies. In this review, we discuss recent findings in relation to the microbiota, particularly in the context of type 1 diabetes.