Monoclonal antibodies either of mouse, mouse/human chimeric, or human origin have been used safely in human trials for a decade. Considerable effort has been committed in investigations of manipulating endogenous immunological activity against tumors and targeting various cytotoxic agents to cancers. These studies have identified several problems that need to be resolved before any such reagents can be used routinely in patients. One of these problems has been the immunogenicity of these monoclonal antibodies. This review article discusses what is known regarding human immune response to monoclonal antibodies and their clinical consequences.