Lactic acid is a decomposed product of anaerobic oxidation of glucose. Recent studies have shown that lactic acid is an important energy substance, signaling molecule, and immunomodulatory molecule, playing a significant role in cellular physiological and pathological processes. In vivo, both histone and non-histone proteins can undergo lactylation modification, thereby participating in the regulation of gene transcription, induction of macrophage polarization, and other processes. The discovery of protein lactylation modification has provided new directions for research on tumors and inflammation. Given the increasing attention paid to lactylation in the study of disease pathogenesis, this article summarizes the research progress of histone and nonhistone lactylation modification, and expound the key roles of lactylation modification in inflammation, cancer, cardiovascular and cerebrovascular diseases, as well as neurodegenerative diseases.