The present invention provides monoclonal antigen-binding proteins that bind to the cardiac glycoside marinobufagenin (MBG), and methods of use. In various embodiments of the invention, the antigen-binding proteins are fully human antigen-binding proteins that bind to MBG. In some embodiments, the antigen-binding proteins of the invention are useful for inhibiting or neutralizing MBG activity, thus providing a means of treating or preventing a MBG-associated disease or disorder selected from the group consisting of hypertension, myocardial fibrosis, uremic cardiomyopathy, heart failure, myocardial infarction, renal failure, renal fibrosis and pre-eclampsia.