The replication cycle of viruses involves entry into host cells, synthesis of virus genes and proteins, assembly of progeny virus particles and their subsequent release. Along with the plasma membrane, viruses also have to interact with the endosomal and vesicular membranes during their replication in host cells. All cellular membranes are composed of lipids and proteins that are usually arranged in various micro domains. During infection of cells by enveloped viruses, the lipids present in both viral and cellular membranes mediate fusion and fission reactions to facilitate virus entry and release. Since non-enveloped viruses do not have a lipid envelope, it is generally believed that their entry mechanism does not involve membrane fusion activity and that these viruses are mainly released by cell lysis. Usually, non-enveloped viruses enter the cells by penetrating the membrane barrier, either via the endocytic pathway using clathrin-coated vesicles, or by the formation of a pore at the cell surface. Recent data obtained from biochemical and structural studies indicate that the overall mechanisms of both entry (Reoviridae) and release of certain non-enveloped viruses (e.g., members of the Picornaviridae and Reoviridae) are analogous to that of enveloped viruses, and that the capsid proteins can function in these activities in a similar manner to the membrane viral proteins. This review discusses the role of lipids in the entry, maturation and release of non-enveloped viruses, focusing mainly on Bluetongue virus (BTV).