NHE-1: Still a viable therapeutic target

► NHE-1 inhibitors protect the ischemic and reperfused myocadium. ► Clinical trials have produced diverse results as well as evidence of adverse effects. ► The bases for clinical results can likely be rationalized based on various factors. ► NHE-1 inhibitors reduce heart failure and improve post-cardiac arrest resuscitation. ► Further development of NHE-1 inhibitors for cardiac therapeutics is warranted.