Adrenergic signaling results from the effects of the catecholamines epinephrine and norepinephrine, on alpha- and beta-adrenergic receptors. In breast cancer, preclinical models suggest that this pathway may influence breast cancer progression through 1) increasing tumor cell survival after exposure to chemotherapeutic agents; 2) increasing breast cancer cell proliferation; and 3) altering the tumor microenvironment in angiogenesis and the inflammatory response. Epidemiologic data have suggested a correlation between drugs that indirectly affect the adrenergic pathway and breast cancer incidence. In addition, there is retrospective evidence suggesting that the use of β-adrenergic blockers in early stage breast cancer patients correlates with an increased time to recurrence. Here we review evidence from both pre-clinical models and epidemiological studies that have examined the question of whether adrenergic signaling may modify breast cancer biology.