Transcription factors orchestrate intricate pathways of cellular growth and differentiation by regulating the rate of transcription of an array of genes. Genetic and biochemical studies have begun to unravel the complex cascade of factors that controls the proliferation and differentiation of cells in the developing pancreas. The specific pathway leading to the development of the insulin-secreting beta cell has been a focus of many of these studies because an understanding of the transcription factors governing this pathway will be crucial to the engineering of new beta cells to cure diabetes. In recent years, the number of transcription factors that has been implicated in beta-cell differentiation and function has grown considerably. Here, we outline the known role of transcription factors in beta-cell development, and describe how these factors form a network of gene activation signals that mediates insulin transcription.