The pathological feature of diabetes, hyperglycemia, is a result of an inadequate number and/or function of insulin producing β cells. Replenishing functional β cells is a strategy to cure the disease. Although β-cell regeneration occurs in animal models under certain conditions, human β cells are refractory to proliferation. A better understanding of both the positive and the negative regulatory mechanisms of β-cell regeneration in animal models is essential to develop novel strategies capable of inducing functional β cells in patients. Zebrafish are an attractive model system for studying β-cell regeneration due to the ease to which genetic and chemical-genetic approaches can be used as well as their high regenerative capacity. Here, we highlight the current state of β-cell regeneration studies in zebrafish with an emphasis on cell signaling mechanisms.