Exhausted and dysfunctional T cells triggered by infection and cancer render the immune system unable to eliminate these pathogens. Pharmacologic blockade of the surface receptors that inhibit T‐cell function has shown remarkable success in patients with various malignancies. In this Review, we discuss the emerging evidence of inhibiting checkpoint pathways as a potential role in controlling or clearing infectious diseases. Though interesting tendencies, much work is still needed in order to develop safe strategies that can be translated into clinically relevant outcomes in patients with infections.