The establishment of human embryonic stem (ES) cells has opened possibilities for cell replacement therapy to treat diseases such as diabetes, Parkinson's disease and cardiac myopathies. Self-renewal is one of the essential defining characteristics of stem cells. If stem cells are to have widespread therapeutic applications, it is essential to identify the extrinsic and intrinsic factors maintaining self-renewal, particularly in culture. Insight into the regulation of known self-renewal transcription factors and cross-talk between their upstream signalling pathways is important for a better understanding of how stem cell self-renewal and differentiation are related to downstream target genes. This may lead to the establishment of protocols for obtaining a large supply of ES cells. Here, we review the role that TGFbeta superfamily members are thought to play in self-renewal and differentiation of human and mouse ES cells. We focus on the prototype TGFbeta, TGFbeta1, activin A, nodal and bone morphogenetic proteins and their expression, activity and function in embryonic stem cells.