The CDKN2B gene locus is altered in up to approximately 60% of bladder cancer, most commonly as a homozygous deletion, and frequently with concurrent deletion of the CDKN2A locus. CDKN2A/CDKN2B loss may be associated with increased sensitivity to CDK4/6 inhibitors. The efficacy and toxicity profiles of these inhibitors in the context of a variety of cancer types are currently under evaluation in clinical trials.