We have learned that genes in mammalian cells are transcribed into messenger RNAs (mRNAs), which are to be translated into polypeptides (proteins). This is known as "Central Dogma." Gene expression must be appropriately maintained to regulate development, differentiation, and proliferation of cells. Imbalances or disturbances in gene expression are sometimes deleterious for living things. For example, steroid and thyroid hormones directly bind to nuclear receptors, which induce expression of specific genes. Recent global analyses of gene transcripts revealed that specific transcription factors (TFs) and their networking systems physiologically correspond to the onset of human diseases, including cancer. In other words, expression of specific genes might have relevance to pathogenesis of diseases. Given that OKSM (Yamanaka) factors convert somatic cells into induced pluripotent stem (iPS) cells, alterations in transcriptional state could affect destiny of the cells. In this chapter, revisiting known TFs, we would argue if transcription controlling strategies could contribute for the novel therapies on human diseases. 2. Transcription factors (TFs) in mammalian cells Transcription factors are divided into two groups. First, the general TFs (GTFs), including preinitiation complex components TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and THIIH, are the primary protein factors that are required for the initiation of transcription from the TATA box (or TATA element), then elongation is executed by RNA polymerase II (RNA pol II) [1]. The others are the site-specific TFs or the DNA sequence-specific binding proteins. 2.1 The GTFs and TATA-less promoters Molecular mechanisms of the initiation of transcription from TATA box have been well known as the most essential nuclear events in mammalian cells. However, about 70% of mammalian gene promoters have no TATA or TATA-like elements, and they are referred to as TATA-less promoters [2]. In yeast cells, most of genes are regulated by the same general TF-dependent system independent of TATA or TATA-like sequences [3]. TATA-containing and TATA-less promoters