PURPOSE: Despite modern reperfusion and pharmacologic therapies, myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. Therefore, the development of further therapeutics affecting post-MI recovery poses significant benefits. This review focuses on the post-MI immune response and immunomodulatory therapeutics that could improve the wound-healing response. METHODS: This narrative review used OVID versions of MEDLINE and EMBASE searching for clinical therapeutics targeting the immune system during MI. Preclinical models and clinical trials were included. Additional studies were sourced from the reference lists of relevant articles and other personal files. FINDINGS: After MI, cardiomyocytes are starved of oxygen and undergo cell death via coagulative necrosis. This process activates the immune system and a multifaceted wound-healing response, comprising a number of complex and overlapping phases. Overactivation or persistence of one or more of these phases can have potentially lethal implications. This review describes the immune response post-MI and any adverse events that can occur during these different phases. Second, we describe immunomodulatory therapies that attempt to target these immune cell aberrations by mitigating or diminishing their effects on the wound-healing response. Also discussed are adult stem/progenitor cell therapies, exosomes, and regulatory T cells, and their immunomodulatory effects in the post-MI setting. IMPLICATIONS: An updated understanding into the importance of various inflammatory cell phenotypes, coupled with new technologies, may hold promise for a new era of immunomodulatory therapeutics. The implications of such therapies could dramatically improve patients' quality of life post-MI and reduce the incidence of progressive heart failure.