Acute kidney injury (AKI) is one of the most common serious complications after cardiac surgery. Although many causes and risk factors have been identified, effective measures to prevent AKI after cardiac surgery are still lacking. Recent randomized trials and meta-analyses suggest a potential role for amino acids in preventing AKI after cardiac surgery. The growing interest in this topic is reflected in the number of recently published meta-analyses, which approaches that of adequately designed clinical trials addressing this subject. However, close examination of these meta-analyses reveals substantial heterogeneity among the included trials, particularly with respect to the selection of amino acids, dosages used, and proposed mechanisms of action. In this review, we describe the putative mechanisms of action, detail the major sources of heterogeneity and identify key gaps that need to be addressed to clarify the role of amino acids in preventing AKI following cardiac surgery.