The recently disclosed plasticity properties of adult-derived stem cells, their ability to be reprogrammed by defined factors into pluripotent stem cells and the comprehension of “epi”-genetic mechanisms underlying stem cells differentiation process has opened unexpected avenues to attempt regeneration of tissues affected by degenerative disorders and prompted the birth of the new “regenerative medicine” concept. Regeneration of the vascular and myocardial tissues is considered a primary endpoint to limit the consequences of acute and chronic ischemic heart disorders. Cellular therapy of the ischemic heart has been attempted in more than 1000 patients worldwide and the results of the first meta-analysis studies have been recently made available. In several cases, the results did not fulfill the expectations. In fact, they unpredictably indicated modest, yet significant, clinical benefits in patients compared to the outstanding results using stem cells in animal models of ischemic heart and peripheral disease. Several interpretations have been raised to explain these discrepancies. These include lifestyle and risk factor-associated modifications of the stem cell biological activity, but also procedural problems in the translation of cells from bench to bedside. The present review will cover light and shaded areas in the cardiovascular cellular therapy field, and will discuss about recent advances and related patents designed to enhance efficiency of stem cell therapy in patients with cardiovascular disease. These advancements will be discussed in the light of the most advanced issues that have been introduced worldwide by Regulatory Agencies.