In this review, we will discuss (i) current knowledge on the molecular basis of efferocytosis as the cornerstone target of novel therapies for stroke and its future directions; (ii) current evidence on the function of CD163 as a game-changing target and a novel biomarker of acute stroke; (iii) molecular pathways and potential targets involved in physical rehabilitation, hypothermia, and IHT after stroke; and (iv) the emerging role of mitochondrial dysfunction and mitochondria-targeted therapies. Here, CD163 is linked to stroke disorder.