Nephrogenic systemic fibrosis (NSF) was first recognized as a complication of gadolinium-based contrast (GBC) exposure in 2006 and confirmed subsequently by numerous investigators. Early information on the toxicity of free gadolinium (Gd3+) and the pharmacokinetics of this agent in patients with underlying kidney disease were likely unrecognized subtle clues to its potential for adverse effects in humans. Since the recognition of NSF as a complication of GBC exposure, our approach to imaging in patients with kidney disease has been altered. As these patients require various forms of imaging to diagnose associated conditions, we must utilize an evidence-based approach to imaging options. It is our responsibility to identify patients at high risk to suffer this complication and choose between non-GBC imaging modalities, radiocontrast-based imaging modalities, and GBC imaging modalities based on risk:benefit assessment. The benefits of rapid, accurate diagnosis must be weighed against risks associated with CT scan with radiocontrast (radiation exposure, allergic contrast reactions, acute kidney injury), GBC imaging (development of NSF), and missed diagnoses due to use of suboptimal imaging modalities in an effort to avoid radiocontrast and GBC agent exposure.