Functions of the immune system are critical for the outcome of gene therapy. Immunologists, virologists, and gene therapists met in Pamplona, Spain, in October 2009 to present and analyze common frontiers in these fields under the auspices of the Ramon Areces Foundation (http://www.fundacionareces.es). Antibodies and cell-mediated immune mechanisms can be either friends or foes in gene therapy. A form of Murphy’s law seems to apply: “If an immune response is to be induced, it will usually be weak. If an immune response is to be avoided, it will be almost always neutralizing.”