Humoral immunity, in particular secreted neutralizing antibodies, is of central importance to protect the body against acutely cytopathic viruses, whereas noncytopathic viruses have found ways of balanced coexistence with the immune system to avoid antibody-mediated elimination. There is evidence that polyspecific "natural" antibodies provide early protection, independent of T cell help. If that line of defense is crossed, T cell-dependent immune responses then generate a humoral memory provided by long-lived plasma cells secreting specific antibodies of adapted avidity and function, i.e., isotype, even in the absence of virus. Secreted protective antibodies of humoral memory provide an efficient line of defense against reinfection and are backed up by specific B and T memory cells of reactive memory. Whereas humoral memory has developed effective antiviral protection, some viruses (i.e., HIV) have managed to develop specific evasion strategies to escape it. Thus, coevolution provides us with some insight into just how substantial antiviral antibodies and memory B cell are in protecting the host from virus infection.