Macrophagic myofasciitis (MMF) is an immune-mediated condition first reported in 1998. MMF is characterized by post-vaccination systemic manifestations as well as local-stereotyped and immunologically active lesion in the site of inoculation (deltoid muscle). MMF systemic symptoms included myalgias, arthralgias, marked asthenia, muscle weakness, chronic fatigue, and fever. Recently, studies demonstrated that the local lesion is due to persistence for years at site of injection of an aluminum (Al(OH)3) adjuvant commonly used in human vaccines. Time elapsed from last immunization with an Al(OH)3-containing vaccine to muscle biopsy range from 3 months to 8 years; in rare cases, MMF may be diagnosed even 10 years post-vaccination. The discrepancy between the wide applications of aluminum hydroxide-containing vaccines and the very limited number of MMF cases reported may be resolved by observations suggesting that aluminum-containing vaccinations may trigger MMF in genetically susceptible subjects carrying the HLA-DRB1*01. Thus, MMF may be defined as an emerging novel condition that may be triggered by exposure to alum-containing vaccines, in patients with a specific genetic background, and this temporal association may be exhibited from a few months up to 10 years.