Since their clinical introduction in 1988, gadolinium-based contrast agents (GBCAs) have demonstrated an excellent safety profile with a reported acute adverse reaction rate ranging from 0.01% to 2%. By comparison, the acute adverse reaction rate of low osmolar nonionic computed tomography contrast agents (CTCs) ranges from 0.7% to 3.1%. Many of the risk factors associated with CTC reactions (drug allergies, asthma, atopy, prior contrast reaction) also point toward an increased incidence of acute adverse events to GBCAs. With CTCs, an increased adverse event rate was associated with ionic preparations and high osmolality. In response to concerns for nephrogenic systemic fibrosis, GBCAs are now selected for their augmented chemical stability. These agents possess some combination of macrocyclic chelates or ionic preparations. With their improved chemical stability, these agents also possess higher osmolality and the increased potential to elicit an acute adverse reaction. In light of these concerns, researchers are now focusing greater efforts on reexamining acute adverse reactions to GBCAs and whether there is an increased association with certain agents. In addition to hypersensitivity reactions, this article will also discuss contrast extravasations, safety of GBCAs for pregnant and nursing patients, and the potential nephrotoxic effects of GBCAs.