Personalized medicine is a medical approach that tailors treatment to individual patients based on their genetic, proteomic, and other omics data. It aims to improve treatment outcomes by considering individual variations in genotype, phenotype, and environmental factors. Protein drugs are crucial in personalized medicine, as they have higher target specificity and biological activity than small-molecule drugs. However, proteins can exist in multiple proteoforms, which can lead to varying drug responses. Proteoformics, the study of proteoforms, is essential for developing personalized drugs that target specific proteoforms, improving drug efficacy and reducing adverse effects. Proteoformics involves high-throughput techniques to identify, characterize, and quantify proteoforms, enabling the development of more effective and personalized therapies. Pharmacogenomics, which studies how genes influence drug responses, is a key component of personalized medicine. The three drug revolutions in history highlight the evolution of drug development, with the third revolution focusing on personalized drug therapy based on proteoforms. Personalized drug therapy has significant benefits, including improved therapeutic effects, reduced adverse reactions, optimized drug selection and dosages, and more efficient use of medical resources. However, challenges remain in the use of proteins as drug targets due to the complexity of proteoforms and the need for further research and experimental verification. Despite these challenges, personalized drug therapy holds great promise for improving patient outcomes and advancing medical research.Personalized medicine is a medical approach that tailors treatment to individual patients based on their genetic, proteomic, and other omics data. It aims to improve treatment outcomes by considering individual variations in genotype, phenotype, and environmental factors. Protein drugs are crucial in personalized medicine, as they have higher target specificity and biological activity than small-molecule drugs. However, proteins can exist in multiple proteoforms, which can lead to varying drug responses. Proteoformics, the study of proteoforms, is essential for developing personalized drugs that target specific proteoforms, improving drug efficacy and reducing adverse effects. Proteoformics involves high-throughput techniques to identify, characterize, and quantify proteoforms, enabling the development of more effective and personalized therapies. Pharmacogenomics, which studies how genes influence drug responses, is a key component of personalized medicine. The three drug revolutions in history highlight the evolution of drug development, with the third revolution focusing on personalized drug therapy based on proteoforms. Personalized drug therapy has significant benefits, including improved therapeutic effects, reduced adverse reactions, optimized drug selection and dosages, and more efficient use of medical resources. However, challenges remain in the use of proteins as drug targets due to the complexity of proteoforms and the need for further research and experimental verification. Despite these challenges, personalized drug therapy holds great promise for improving patient outcomes and advancing medical research.