Nitrogen (N) is an essential macronutrient for plants. In nature, N cycles between different inorganic and organic forms some of which can serve as nutrients for plants. The inorganic N forms nitrate and ammonium are the most important sources of N for plants. However, plants can also uptake and use organic N forms such as amino acids and urea. Besides their nutritional role, nitrate and other forms of N can also act as signals that regulate the expression of hundreds of genes causing modulation of plant metabolism, physiology, growth, and development. Although many genes and processes affected by changes in external or internal N have been identified, the molecular mechanisms involved in N sensing and signaling are still poorly understood. Classic reverse and forward genetics and more recently the advent of genomic and systems approaches have helped to characterize some of the components of the signaling pathways directing Arabidopsis responses to N. Here, we provide an update on recent advances to identify the components involved in N sensing and signaling in Arabidopsis and their importance for the plant response to N. (C) 2010 John Wiley & Sons, Inc. WIREs Syst Biol Med 2010 2 683-693