Autophagy is a highly conserved intracellular degradation process that targets protein aggregates and damaged organelles. Autophagy is also implicated in numerous viral infections, including human immunodeficiency virus-1 (HIV-1), influenza A (IAV) and herpes simplex virus-1 (HSV-1). Depending on the virus, autophagy can restrict or promote viral replication, and play key roles in modulating inflammation and cell survival. In this review, we consider examples of autophagy-virus interplay, highlighting the protective role of autophagy in human infections. We summarize recent discoveries and emerging themes illuminating autophagy’s role in immunity and inflammation upon viral infection. Finally, we discuss future prospects and therapeutic implications, and potential caveats associated with using autophagy to control viral infections in humans.