The ability to regenerate missing body parts is one of the great mysteries of biology and is found throughout the animal kingdom. This ability has been studied for centuries, yet satisfying explanations for how it occurs have been elusive. How do some animals regenerate and why can’t we? Our focus is to address this question by seeking the cellular and molecular basis for regeneration in highly regenerative organisms. Much of our work utilizes planarians, a classic regeneration model. We seek general regeneration principles by studying additional regenerative organisms and by developing novel model systems. To address how animals determine which tissue types to regenerate, we seek and study the instructions that guide regeneration. In planarians and acoels, we found coordinate systems of positional information guiding regeneration, involving regional expression of signaling molecules in muscle. We study the functions of such systems and how positional information is regenerated following injury. To address how missing cell types are generated in an adult tissue context, we study the cells that generate new cell types. In planarians, such cells are called neoblasts, which constitute a population of proliferative cells that includes pluripotent stem cells. We study how these stem cells choose their fates and generate new cells that produce tissue patterns in regeneration.