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Multiple therapeutic strategies are being explored including small molecules, gene delivery, and stem cells; however, tissue engineering remains a primary approach to achieving regeneration. Organ transplantation demonstrates that damaged tissues can be replaced, but technology to regenerate complex organs <jats:italic>de novo<\/jats:italic> is not yet available. Instead, tissue engineering can augment the body's own regenerative ability by replacing tissue sections and enhancing the regenerative cascade. As a consequence of these opportunities, it is timely to review the criteria and current status of engineered tissue grafts designed as patches to replace or regenerate damaged or diseased tissue and restore organ function. This topic will be explored starting from the biomaterials and cells incorporated into the engineered graft, the environment into which the graft is implanted and the integration of the engineered graft with the host. Common issues will be addressed that are relevant to regeneration in multiple tissue and organ systems. Specific examples will focus on engineered grafts for myocardial and corneal repair to illustrate the tissue\u2010specific challenges and opportunities and highlight the innovation needed as the field moves forward. <jats:italic>WIREs Syst Biol Med<\/jats:italic> 2012, 4:207\u2013220. doi: 10.1002\/wsbm.164<\/jats:p><jats:p>This article is categorized under:\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Developmental Biology &gt; Stem Cell Biology and Regeneration<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Translational, Genomic, and Systems Medicine &gt; Therapeutic Methods<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Translational, Genomic, and Systems Medicine &gt; Translational 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