The National Cancer Institute estimates that approximately 13.7 million Americans with a history of cancer were alive on January 1, 2012. With the rising number of cancer survivors, there is an increased focus on how chemotherapy agents modulate the cardiovascular biology and cause chemotherapy-related heart failure in certain patients. Neuregulin-1 (NRG-1) is an important cardiac growth factor that is essential for normal myocardial development and maintenance. Certain chemotherapy agents perturb the normal NRG-1 signaling in the cardiovascular system and cause cardiac dysfunction and, in some cases, symptomatic heart failure. As researchers have learned the critical importance of NRG-1 within the cardiovascular system, more attention has been focused on the potential use of NRG-1 as biomarker and therapy for the treatment of heart failure. This review will highlight the biology of NRG-1 within the cardiovascular system, its role in chemotherapy-induced heart failure, and the translational potential of NRG-1 as treatment for heart failure. © Springer Science+Business Media 2014.