Phytohormone ethylene has profound effects on growth and development in plants. Molecular genetic studies using Arabidopsis have defined a linear pathway for ethylene signal transduction leading from initial hormone perception to changes in gene expression. Ethylene is perceived by a family of ethylene receptor complex at endoplasmic reticulum (ER), which negatively regulates the ethylene response. Ethylene binding inactivates the receptors and represses the Raf-like kinase CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) that actively represses ethylene response pathway in the absence of ethylene. Consequently, the ETHYLENE INSENSITIVE2 (EIN2), a membrane protein with similarities to Nramp metal ion transporter becomes activated and positively regulates the ethylene signaling pathway by transmitting the signal into the nucleus. Finally, the nuclear signal initiates the transcriptional cascade via the transcription factors ETHYLENE INSENSITIV3/ETHYLENE INSENSITIVE3-LIKE proteins (EIN3/EILs). This review will summarize the up-to-date understanding of ethylene signal transduction, in aiming to illustrate how challenges in hormone biology have been resolved through the power of molecular genetics and to provide references for interested readers searching for further information.