Early growth response-1 (Egr-1) is a Cys2-His2-type zinc-finger transcription factor. A broad range of extracellular stimuli is capable of activating Egr-1, thus mediating growth, proliferation, differentiation or apoptosis. Egr-1 is, therefore, participating in the progression of a variety of diseases such as atherosclerosis or cancer. Functional response elements connect Egr-1 to signal transduction cascades targeting Egr-1. Five serum response elements (SRE) have been identified in the promoter region of Egr-1, the binding region of serum response factor (SRF). The Rho/Rho-kinase pathway has been shown to regulate actin reorganization via LIM-kinase mediated cofilin phosphorylation. Recent studies have revealed that the actin binding striated muscle activator of Rho signaling (STARS) promotes translocation of myosin related transcription factors (MRTFs) into the nucleus, leading to SRF activation. The ternary complex factor (TCF) Elk-1 eventually bridges the gap between SRF-mediated gene transcription and the Raf/MEK/ERK pathway. Moreover, the Egr-1 promoter owns two cAMP response elements (CREs), whose relevance for gene expression is still unclear. An Egr-1 binding site (EBS) located on the Egr-1 promoter itself is arguing for a negative feedback mechanism. The acquired knowledge on transcriptional regulation of Egr-1 is not entirely understood. In this review, we highlight upstream and downstream signaling in vitro and in vivo associated with Egr-1.