L-Arginine is the biological precursor of nitric oxide (NO), which serves as an important signal and effector molecule in animals. This review summarizes some structure-function aspects of the mammalian nitric oxide synthases, which are enzymes that catalyze the oxidation of L-arginine to NO and L-citrulline. These include aspects related to: 1) the chemical transformations of L-arginine during enzyme catalysis, 2) binding of L-arginine or its structural analogs to the nitric oxide synthases, and 3) how L-arginine levels may affect product formation by the nitric oxide synthases and how this can be modulated by structural analogs of L-arginine.