Clinical trials and animal studies showed that ingestion of soy proteins improves blood lipid profiles including lowering triglyceride, total and LDL cholesterol levels and increasing HDL cholesterol content. However, the effective components in the soy and the mechanisms involved in the hypolipidemic actions are not fully understood. Increasing evidence from animal studies have suggested that soy components may regulate lipid metabolism by modulating the activities of key transcription factors and thereby changing the downstream gene expression involved in lipogenesis or lipolysis. It has been shown that intake of soy proteins alters the expression of genes for sterol regulatory element binding protein, peroxisomal proliferator activated receptor, and liver X receptor. Dietary soy proteins suppress the DNA binding activities of hepatic nuclear receptors for thyroid hormones and retinoic acid, and alter the activities of key enzymes including cholesterol 7alpha hydroxylase and ATPase/ATP synthase through post-translational protein modifications. This paper reviews the current understanding of the cellular and molecular events by which soy components affect lipid levels, especially focusing on modulation of transcription factors and regulation of gene expression involved in lipid metabolism by soy proteins and associated isoflavones.