Myeloid-derived suppressor cells (MDSCs) are a population of myeloid-derived cells with specific markers and immunosuppressive functions. MDSCs can enrich under pathological conditions (e.g., advanced cancer, sepsis, and chronic infection) and suppress the proliferation, activation, and migration of T lymphocytes and other immune cells. The frequencies of MDSCs are significantly associated with disease development and patient outcomes. Through new detection methods including single cell sequencing and mass spectrometry, researchers have found significant differences in phenotypic markers, genetic expression, metabolism, and regulatory pathways between MDSCs and normal myeloid cells. Abundant achievements have been also obtained on therapies targeting MDSCs especially in cancer research. In this review, we start with milestones in MDSCs research, focus on the mechanisms of therapies targeting MDSCs and their roles in infectious diseases, and summarize recent achievements in MDSCs research.