Polyamines are small, abundant, aliphatic molecules present altogether mammalian cells. Within the context of the cell, they play a myriad of roles, from modulating macromolecule conformation to promoting cellular proliferation and signaling. In addition, polyamines have emerged as important molecules in virus-host interactions. Polyamines are polycations that interact with charged molecules like DNA, RNA and proteins. They play multiple roles in cell growth, survival and proliferation. Changes in polyamine levels are related to aging and diseases. Their levels decline continuously with age and polyamine supplementation increases life span in model organisms. Polyamines have also been involved in stress resistance. They can increase life span and delay kidney glomerular atrophy. The various studies have also shown mainly positive effects of polyamines on stress resistance. In plants, exogenous spermine treatment and increased polyamine synthesis by genetic means cause higher stress resistance. High levels of polyamines are associated with many diseases, including cancers. In these cases, polyamines have mostly been thought of as exacerbating, if not causal, factors. The success of these approaches has led to the search for additional host factors that could be drug targeted to limit virus replication. Among many promising potential host targets that are described to be important for virus replication, recent studies have revived interest within the role of polyamines in virus replication. Polyamines have now been suggested to possess a task within the replication of viruses across all known viral replication strategies and most viral families.