One of the principal complications of radiographic procedures utilizing intravascular iodinated contrast media is acute kidney injury. Although several clinical and procedural factors impact a patient's risk for contrast-induced acute kidney injury (CIAKI), substantial attention has been focused on the relationship between the type of contrast agent used and renal injury. Multiple contrast agents are available for clinical use, each defined by a series of physicochemical properties. The evolution from high osmolal to low osmolal and, more recently, iso-osmolal contrast media has led to several clinical trials and meta-analyses comparing the nephrotoxicity of different contrast agents. This article summarizes the physicochemical properties that define and differentiate iodinated contrast media, discusses the purported relationship between these properties and kidney injury, and describes the salient findings of clinical trials and meta-analyses that have compared the nephrotoxic effects of contrast agents. Although ongoing and future studies will further elucidate our understanding of the relationship between iodinated contrast and risk for CIAKI, a sound understanding of the currently available data will help inform evidence-based decisions on the use of these agents in clinical practice.