Treatment of ischemic heart disease has evolved considerably over time, seeing a technological impetus in recent times. Prompt diagnosis and progressively earlier reperfusion of the infarct artery have become the cornerstone of the early myocardial ischemia management. However, treatment of post-infarction sequelae resulting from ischemic damage sustained within the myocardium remains a considerable challenge. In this setting, stem cell therapy has emerged as an exciting regenerative modality with a promise to arrest or even reverse the pathological myocardial remodeling. Multiple preclinical and clinical studies have thereafter reported use of various types of stem cells delivered through varying routes. While most of these studies reported positive results, some appropriate concerns were raised in others. This has resulted in considerable uncertainty regarding cell therapy and an inability to formulate therapeutic recommendations. Though there has been a considerable improvement in our understanding of stem cell properties, there is a need to identify specific mechanisms of actions in order to maximize the benefits of stem cell therapy in ischemic heart disease. With this review, we attempt to highlight some of the salient features of stem cell research, focusing on understanding the predominant types of stem cells, proposed mechanisms of action, routes of administration, and application of this exciting and innovative regenerative therapy offered by stem cells.