Continuing developments from the study of cancer at the molecular level are yielding increasing numbers of targets that may be used for therapeutic intervention. Advances in the field of antibody engineering over the past several decades have given scientists the capability of directing the highly specific interaction of antibodies with antigens inward, to the intracellular compartments of living cells. These intracellular antibodies, i.e., intrabodies, are being developed to bind to, neutralize, or modify the function or localization of cancer-related targets and thereby affect the malignant phenotype. This has resulted in a promising new tool for the study and treatment of cancer. Due to recent advances in the development of the antibody engineering technologies, increasing numbers of intrabodies are being exploited to a growing list of cancer-related, as well as other disease targets. There are still, however, many technical issues, particularly related to clinical applications of the intrabodies, that must be addressed before the full promise of this class of therapeutic agent is realized. This review will focus on the recent progress in the generation and use of intrabodies in the field of oncology. The technical issues associated with their further development will also be discussed.