Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that causes a wide range of infections, from mild to life-threatening, including pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. Recurrent GAS infections can lead to severe autoimmune sequelae, such as rheumatic fever and rheumatic heart disease, which are major causes of morbidity and mortality, particularly in children and the elderly. Antibiotics are the primary treatment for early GAS infections, but increasing resistance to penicillin and macrolides poses a significant challenge. Vaccination is considered the most effective medical intervention against infectious diseases, and recent advances in GAS vaccine development have focused on identifying key virulence factors, such as the M protein, hyaluronic acid capsule, and pyrogenic toxins, to design effective vaccines. The M protein is a major virulence factor of GAS, inhibiting phagocytosis and enabling bacterial survival. It is composed of multiple regions, including the N-terminal and C-terminal, with the C-terminal region being more conserved and suitable for vaccine development. The hyaluronic acid capsule also plays a critical role in immune evasion by preventing phagocytosis. Other virulence factors, such as streptolysin S (SLS), streptolysin O (SLO), and SpeB, contribute to bacterial colonization and pathogenesis. Recent advances in GAS vaccine development include the use of peptide-based subunit vaccines, which target conserved regions of the M protein and other virulence factors. These vaccines aim to induce strong adaptive immunity and protect against GAS infections. Preclinical studies have shown promising results with various vaccine candidates, including those based on the M protein, hyaluronic acid capsule, and other antigens. Clinical trials are ongoing, with some vaccines entering phase I and II trials, showing safety and efficacy. Despite these advances, challenges remain in developing a universal GAS vaccine, including the need for effective adjuvants, the diversity of GAS strains, and the risk of autoimmune complications. Global efforts are needed to support preclinical and clinical trials to identify a safe and effective GAS vaccine.Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that causes a wide range of infections, from mild to life-threatening, including pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. Recurrent GAS infections can lead to severe autoimmune sequelae, such as rheumatic fever and rheumatic heart disease, which are major causes of morbidity and mortality, particularly in children and the elderly. Antibiotics are the primary treatment for early GAS infections, but increasing resistance to penicillin and macrolides poses a significant challenge. Vaccination is considered the most effective medical intervention against infectious diseases, and recent advances in GAS vaccine development have focused on identifying key virulence factors, such as the M protein, hyaluronic acid capsule, and pyrogenic toxins, to design effective vaccines. The M protein is a major virulence factor of GAS, inhibiting phagocytosis and enabling bacterial survival. It is composed of multiple regions, including the N-terminal and C-terminal, with the C-terminal region being more conserved and suitable for vaccine development. The hyaluronic acid capsule also plays a critical role in immune evasion by preventing phagocytosis. Other virulence factors, such as streptolysin S (SLS), streptolysin O (SLO), and SpeB, contribute to bacterial colonization and pathogenesis. Recent advances in GAS vaccine development include the use of peptide-based subunit vaccines, which target conserved regions of the M protein and other virulence factors. These vaccines aim to induce strong adaptive immunity and protect against GAS infections. Preclinical studies have shown promising results with various vaccine candidates, including those based on the M protein, hyaluronic acid capsule, and other antigens. Clinical trials are ongoing, with some vaccines entering phase I and II trials, showing safety and efficacy. Despite these advances, challenges remain in developing a universal GAS vaccine, including the need for effective adjuvants, the diversity of GAS strains, and the risk of autoimmune complications. Global efforts are needed to support preclinical and clinical trials to identify a safe and effective GAS vaccine.