© 2018 Elsevier Ltd. All rights reserved. The heart is responsible for providing blood flow to enable perfusion of all tissues and organs with oxygen and nutrients, and is, due to its high oxygen demand and continuous action, particularly susceptible to hypoxia and perfusion deficits. Since the heart is unable to cope with tissue damage and no curative treatment is available, researchers are actively investigating novel therapeutic strategies for cardiac regeneration. Cardiac cell therapy and tissue engineering have attracted considerable attention and clinical trials are ongoing to assess clinical efficacy and accommodate translation to the clinic. In addition, cardiac toxicity as a result of drug therapy is one of the main causes of compound attrition during drug development and post-marketing withdrawal. Moreover, although some cardiotoxicity assays have become standard in drug development, these assays require further improvement as they are prone to false-positive and false-negative outcomes. Stem cell and tissue engineering technologies have been proposed as potential tools for addressing these limitations. In this chapter, we will discuss current developments within these fields and make recommendations for future work.