Asparagine biosynthesis and breakdown are tightly regulated in mammalian cells. Recent studies indicate that asparagine supply could be a limiting factor for the replication of some viruses such as vaccinia virus and human cytomegalovirus. In this Viewpoint, we highlight the importance of asparagine metabolism during virus replication and rationalize that asparagine metabolism could be a viable target for broad-spectrum antiviral development. To achieve this goal, more studies into asparagine metabolism during viral infections are demanded. These efforts would benefit beyond viral diseases, as asparagine supply is also a limiting factor in various stages of cancer development.