The adrenergic system is an essential regulator of cardiovascular, endocrine, neuronal, vegetative, and metabolic function. The biological effects of the endogenous catecholamines epinephrine and norepinephrine are mediated by nine distinct G protein-coupled receptor subtypes. These adrenergic receptors can be divided into three different groups, the a1-receptors (α1A, α1B, α1D), α2-receptors (α2A, α2B α2C) β-receptors (β1, β2, β3). In the absence of sufficiently subtype-selective ligands, transgenic mouse models with targeted deletions in the individual receptor genes as well as mouse lines with tissue-specific overexpression of adrenergic receptors have been generated recently. Most adrenergic receptor subtypes have distinct physiological functions. Within the α2 receptor group, α2A- and α2C-receptors operate together to control catecholamine release from adrenergic neurons, whereas α2B-receptors are essential for angiogenesis in the developing placenta. Transgenic models of β1- and β2-adrenergic receptors in the heart have revealed differences in signal transduction between these receptors. Whereas both receptors may increase cardiac contractility, chronic signaling via β1-receptors in cardiac myocytes causes hypertrophy, fibrosis, and heart failure. The a1-adrenergic receptor subtypes α1A, α1B, α1D are primarily involved in the regulation of vascular tone and may have partially overlapping functions in vivo. Transgenic mouse models have revealed a number of novel and distinct physiological functions for adrenergic receptors, neurotransmitter transporters, and enzymes, and they may lead to novel therapeutic applications for subtype-selective drugs.