The transcription factor Signal Tranducer and Activator of Transcription 5 (STAT5) plays an important role in many biological processes. To study STAT5 biology, several different constructs have been designed that render STAT5 constitutively active. These constructs have now been used to generate animal models that allow for targeted expression of constitutively active STAT5 including a model where STAT5 is expressed in developing B and T cells. Herein we briefly describe the design of constitutively active STAT5 constructs and recent advances in their use.