Recent clinical trials of active vaccination against beta-amyloid (Abeta) have succeeded in clearing Abeta plaques; however, further understanding of immunization with regards to inflammation and other hallmarks of Alzheimer's disease pathology is required. Antibodies generated with this first-generation vaccine may not have had the desired therapeutic properties or targeted the 'correct' mechanism, but they have opened the way for new clinical approaches, which are now under consideration. Passive administration of monoclonal antibodies directed to various regions of Abeta peptide and/or administration of immunoconjugates of only small fragments of the N-terminal region may lead to the development of an improved second generation of Abeta vaccines. Amyloid immunotherapy offers genuine opportunities for disease treatment; however, such an approach towards treating and preventing Alzheimer's disease patients requires careful antigen and antibody selection to maximize efficacy and minimize adverse events.