Embryonic stem cell (ESC) research is a promising area of investigation with enormous therapeutic potential. We have injected murine wild type (WT) ESCs into a variety of mutant murine blastocysts, which are predisposed to develop a human-like disease, such as muscular dystrophy or the embryonic lethal "thin myocardial syndrome". In this review, we summarize data indicating that partial incorporation of ESCs is sufficient to prevent disease from occurring. We also present data indicating that blastocyst incorporation of ESCs may aid in the prevention of heart failure in stressed WT mice. In some cases, the rescue observed is predominantly non-cell autonomous and relies on the production of secreted factors from the ES-derived cells, but in others, cell replacement is required. Thus, congenital or acquired disease can be pre-emptively averted in mice by developmental injection of ESCs.