Foamy viruses (FVs), a unique type of retroviruses, are characterized by several unusual features in their replication strategy. FVs, common to all non-human primates and several other species, display an extremely broad tropism in vitro. Basically, all mammalian cells and species examined, but also cells of amphibian or bird origin, are permissive to FV glycoprotein (Env)-mediated capsid release into the cytoplasm. The nature of the broadly expressed, and potentially evolutionary conserved, FV entry receptor molecule(s) is poorly characterized. Although recent data indicate that proteoglycans serve as an important factor for FV Env-mediated target cell attachment, additional uncharacterized molecules appear to be essential for the pH-dependent fusion of viral and cellular lipid membranes after endocytic uptake of virions. Furthermore, FVs show a very special assembly strategy. Unlike other retroviruses, the FV capsid precursor protein (Gag) undergoes only very limited proteolytic processing during assembly. This results in an immature morphology of capsids found in released FV virions. In addition, the FV Gag protein appears to lack a functional membrane-targeting signal. As a consequence, FVs utilize a specific interaction between capsid and cognate viral glycoprotein for initiation of thebudding process. Genetic fusion of heterologous targeting domains for plasma but not endosomal membranes to FV Gag enables glycoprotein-independent particle egress. However, this is at the expense of normal capsid morphogenesis and infectivity. The low-level Gag precursor processing and the requirement for a reversible, artificial Gag membrane association for effective pseudotyping of FV capsids by heterologous glycoproteins strongly suggest that FVs require a transient interaction of capsids with cellular membranes for viral replication. Under natural condition, this appears to be achieved by the lack of a membrane-targeting function of the FV Gag protein and the accomplishment of capsid membrane attachment through an unusual specific interaction with the cognate glycoprotein.