HIV-1 remains a chronic viral infection of global health importance. Although HIV-1 replication can be controlled by antiretroviral therapy (ART), there is no cure due to persistence of a long-lived latent reservoir. In addition, people living with HIV-1 who are taking ART still bear signatures of persistent immune activation that include continued type 1 interferon (IFN) signaling. Paradoxically, type 1 IFN exerts a limited role on the control of chronic HIV-1. Indeed, recent reports from humanized mice suggest that type 1 IFN may partly maintain the latent reservoir. In this review, we discuss the molecular interactions between HIV-1 and the type 1 IFN signaling pathway, and examine the efficacy of type 1 IFNs in vivo. We also explore whether limited type 1 IFN manipulation may have a therapeutic role.