In the effort of improving treatment for cardiovascular disease (CVD), scientists struggle with the lack of the regenerative capacities of finally differentiated cardiovascular tissues. In this context, the advancements in regenerative medicine contributed to the development of cell-based therapies as well as macro- and micro-scale tissue-engineering technologies. The current experimental approaches focus on different regenerative strategies including a broad spectrum of techniques such as paracrine-based stimulation of autologous cardiac stem cells, mesenchymal cell injections, 3D microtissue culture techniques and vascular tissue-engineering methods. These potential next-generation strategies are leading the way to a revolution in addressing CVD, and numerous studies are now undertaken to assess their therapeutic value. With this review, we provide an update on the current research directions, on their major challenges, limitations, and achievements.