Besides mediating primary hemostasis and thrombosis, platelets play a critical role in tissue repair and regeneration. They regulate fundamental mechanisms involved in the healing process including cellular migration, proliferation, and angiogenesis. Control of apoptosis/cell survival and interaction with progenitor cells, which are clinically relevant but poorly understood aspects of platelets in tissue repair, will be highlighted in this review. Gaining deeper insight into the less well-characterized molecular mechanisms is necessary to develop new therapeutic platelet-based options.