Heat shock factor (HSF) 1 is a positive regulator of heat shock protein (HSP) genes during stress response. We review studies showing that HSF1 is also involved in regulation of non-heat shock genes. We show that HSF1 represses transcription of genes involved in cell proliferation, differentiation, and monocyte/macrophage activation. We present data suggesting that HSF1 mediates transcriptional repression through both DNA binding dependent and independent manners, involving protein interaction with other transcription factors. The evidence suggests that HSF1 is actively involved in general transcriptional regulation.