Recent studies suggest that alterations of the arginine metabolome and a dysregulation of nitric oxide (NO) homeostasis play a role in the pathogenesis of asthma. L-Arginine, a semi-essential amino acid, is a common substrate for both the arginases and NO synthase (NOS) enzyme families. NO is an important vasodilator of the bronchial circulation, with both bronchodilatory and anti-inflammatory properties, and is synthesized from oxidation of its obligate substrate L-arginine, which is catalyzed by a family of NOS enzymes. Arginase is an essential enzyme in the urea cycle, responsible for the conversion of arginine to ornithine and urea. The NOS and arginase enzymes can be expressed simultaneously under a wide variety of inflammatory conditions, resulting in competition for their common substrate. Although much attention has been directed towards measurements of exhaled NO in asthma, accumulating data show that low bioavailability of L-arginine also contributes to inflammation, hyperresponsiveness and remodeling of the asthmatic airway. Aberrant arginine catabolism represents a novel asthma paradigm that involves excess arginase activity, elevated levels of asymmetric dimethyl arginine, altered intracellular arginine transport, and NOS dysfunction. Addressing the alterations in arginine metabolism may result in new strategies for treatment of asthma.