The prevention of surface fouling is becoming increasingly important for the development of anti-infective medical implants, biosensors with improved signal-to-noise ratios, and low-fouling membranes to name a few examples. We review a direct comparison of poly(ethylene glycol), the gold standard polymer to impart surfaces with nonfouling properties, to an alternative polymer, poly(2-methyl-2-oxazoline) (PMOXA), and show that both polymers are equally excellent in rendering surfaces nonfouling while PMOXA coatings are more stable in oxidative environments. We discuss prerequisites for the fabrication of nonfouling surface coatings and implications for the polymer choice according to application requirements.