The paradigm that the vaginal microbiota is a protective gateway for the urinary and reproductive systems has endured for more than a century and driven decades of probiotic research. Evidence robustly supports the notion that healthy urogenital microbiomes are predominantly colonized by lactobacilli, particularly Lactobacillus crispatus, which can acidify the local environment and protect against urogynecologic pathogen colonization. However, recent studies are beginning to delve deeper into the intricate mechanistic interactions connecting the microbiome, its diverse functional potential, host immunity, pathogens, and the development of urogenital diseases. Leveraging these emerging insights alongside past successes presents promising opportunities for future therapies aimed at enhancing the management of conditions such as bacterial vaginosis, urinary tract infections, bladder pain, urinary incontinence, and beyond.