Transcriptional networks orchestrate fundamental biological processes, including hematopoiesis, in which hematopoietic stem cells progressively differentiate into specific progenitors cells, which in turn give rise to the diverse blood cell types. Whereas transcription factors recruit coregulators to chromatin, leading to targeted chromatin modification and recruitment of the transcriptional machinery, many questions remain unanswered regarding the underlying molecular mechanisms. Furthermore, how diverse cell type-specific transcription factors function cooperatively or antagonistically in distinct cellular contexts is poorly understood, especially since genes in higher eukaryotes commonly encompass broad chromosomal regions (100 kb and more) and are littered with dispersed regulatory sequences. In this article, we describe an important set of transcription factors and coregulators that control erythropoiesis and highlight emerging transcriptional mechanisms and principles. It is not our intent to comprehensively survey all factors implicated in the transcriptional control of erythropoiesis, but rather to underscore specific mechanisms, which have potential to be broadly relevant to transcriptional control in diverse systems.