Memory T cells that mediate fast and effective protection against reinfections are usually generated upon recognition on foreign Ags. However, a "memory-like" T-cell population, termed virtual memory T (T-VM) cells that acquire a memory phenotype in the absence of foreign Ag, has been reported. Although, like innate cells, T-VM cells reportedly play a role in first-line defense to bacterial or viral infections, their protective or pathological roles in immune-related diseases are largely unknown. In this review, we discuss the current understanding of T-VM cells, focusing on their distinct characteristics, immunological properties, and roles in various immune-related diseases, such as infections and cancers.