Cutaneous side-effects associated with immune checkpoint blockade occur in more than half of patients treated with CTLA-4 and PD-1 inhibitors, and are frequently encountered by dermatologists. The molecular mechanism of cutaneous side-effects is incompletely understood but holds important clues about immune tolerance and the antitumor immune response in the skin. A new landmark study published in Nature suggests a critical functional role for the checkpoint receptor PD-1 in restraining self-reactive T cells, which could help explain how some checkpoint-associated cutaneous side-effects arise.