The MiT/TFE family of proteins are important regulators of a number of metabolic processes. One of their most important roles is activating the autophagy pathway in the setting of nutrient deprivation or buildup of toxic metabolites. Their proper and improper functioning in this role has been linked to several types of disease, including cancer and multiple forms of neurodegeneration. In this review we will briefly outline what is known about individual family members’ roles in regulating autophagy across a variety of contexts.