Syphilitic nephropathy is a rare complication of syphilis, caused by the bacterium Treponema pallidum. Syphilis progresses through four stages: primary, secondary, latent, and tertiary, with kidney involvement mainly observed in secondary syphilis. The most frequent histologic pattern observed in syphilis is membranous glomerulonephritis, characterized by proteinuria and edema, with rapid improvement following antibiotic treatment. Other kidney conditions include segmental glomerulosclerosis, rapidly progressive glomerulonephritis, and tubulointerstitial nephritis. Congenital syphilis can also lead to nephrotic syndrome in infants. Co-infections with HIV or viral hepatitis can complicate diagnosis and treatment. Immunohistopathological findings reveal immune complex deposition in the kidneys, further emphasizing the disease’s complexity. The chapter highlights the importance of early diagnosis and treatment, as syphilitic nephropathy typically responds well to penicillin. However, its ability to mimic other diseases makes screening for syphilis crucial in unexplained renal disorders.