High-affinity human anti-viral antibodies [e.g. for human immunodeficiency virus type 1 (HIV-1), respiratory syncytial virus (RSV) and herpes simplex virus (HSV)] can be selected from immune phage-display libraries using a variety of strategies. A small subset of these antibodies show potent neutralization in vitro and anti-viral efficacy in vivo in animal models. The affinities of such antibodies arising from secondary or higher order immune responses can be improved using "CDR walking'. Sequential and parallel optimization variants of this strategy have been used to improve the affinity of a prototype anti-HIV-1 antibody 420-fold. Ultra-high-affinity human antibodies could constitute a new class of useful anti-viral reagents.