The seminal finding that immunization with amyloid-beta 1-42 in Alzheimer's disease (AD) mouse model prevented formation of and/or cleared amyloid plaques has led to numerous studies exploring related approaches for AD and other conformational degenerative disorders. While clinical trials in AD patients were discouraging because of serious side effects, this approach remains promising in light of recent findings in animal models, in which refinements aimed at reducing potential adverse reactions continue to lead to cognitive improvements. In addition to AD and its models, this type of therapy has primarily been assessed in prion disease with positive results, further supporting the potential of immunotherapy for a variety of protein-related diseases in which clearance of the pathogenic agent is likely to alleviate symptoms.