This review discusses key microbiological and immunological aspects of lower urinary tract inflammation and infection, focusing on urethritis, interstitial cystitis/bladder pain syndrome (IC/BPS), urinary tract infections (UTIs), and urosepsis. The lower urinary tract, including the urethra and bladder, is frequently exposed to pathogens, and its immune defenses involve mechanical and physiological barriers, antimicrobial peptides, and immune cells. The urinary tract microbiome, though previously thought to be sterile, is now recognized as having a low-biomass microbiome that may influence health and disease. Urethritis, often caused by sexually transmitted infections (STIs) or UTIs, is characterized by urethral inflammation and symptoms such as discharge and dysuria. It is classified as gonococcal (GU) or non-gonococcal (NGU), with various pathogens involved. Treatment strategies include empirical therapy and nucleic acid amplification tests for accurate diagnosis. However, increasing resistance to antibiotics, particularly to macrolides, poses challenges in managing NGU. IC/BPS is a family of inflammatory bladder conditions with varying subtypes, including Hunner type (HIC) and BPS. Diagnosis relies on symptom profiles and exclusion of other conditions. Management includes conservative strategies, surgical interventions, and pharmacological therapies such as pentosan polysulfate and dimethyl sulfoxide. Novel therapies, including liposome-based treatments and cannabinoids, are being explored. IC/BPS may be linked to systemic conditions and functional somatic syndromes, highlighting the need for further research. UTIs are classified as uncomplicated or complicated, with the bladder and kidneys being the most common sites. They are often caused by uropathogenic E. coli (UPEC), and treatment involves antibiotics, though resistance is a growing concern. Asymptomatic bacteriuria (ASB) is common but not typically treated. Non-antibiotic therapies, such as cranberry products and Canephron N, show some efficacy but are not as effective as antibiotics. The review emphasizes the importance of understanding the microbiological and immunological aspects of lower urinary tract infections to develop effective therapeutic strategies and address challenges such as antimicrobial resistance and the need for better diagnostic tools.This review discusses key microbiological and immunological aspects of lower urinary tract inflammation and infection, focusing on urethritis, interstitial cystitis/bladder pain syndrome (IC/BPS), urinary tract infections (UTIs), and urosepsis. The lower urinary tract, including the urethra and bladder, is frequently exposed to pathogens, and its immune defenses involve mechanical and physiological barriers, antimicrobial peptides, and immune cells. The urinary tract microbiome, though previously thought to be sterile, is now recognized as having a low-biomass microbiome that may influence health and disease. Urethritis, often caused by sexually transmitted infections (STIs) or UTIs, is characterized by urethral inflammation and symptoms such as discharge and dysuria. It is classified as gonococcal (GU) or non-gonococcal (NGU), with various pathogens involved. Treatment strategies include empirical therapy and nucleic acid amplification tests for accurate diagnosis. However, increasing resistance to antibiotics, particularly to macrolides, poses challenges in managing NGU. IC/BPS is a family of inflammatory bladder conditions with varying subtypes, including Hunner type (HIC) and BPS. Diagnosis relies on symptom profiles and exclusion of other conditions. Management includes conservative strategies, surgical interventions, and pharmacological therapies such as pentosan polysulfate and dimethyl sulfoxide. Novel therapies, including liposome-based treatments and cannabinoids, are being explored. IC/BPS may be linked to systemic conditions and functional somatic syndromes, highlighting the need for further research. UTIs are classified as uncomplicated or complicated, with the bladder and kidneys being the most common sites. They are often caused by uropathogenic E. coli (UPEC), and treatment involves antibiotics, though resistance is a growing concern. Asymptomatic bacteriuria (ASB) is common but not typically treated. Non-antibiotic therapies, such as cranberry products and Canephron N, show some efficacy but are not as effective as antibiotics. The review emphasizes the importance of understanding the microbiological and immunological aspects of lower urinary tract infections to develop effective therapeutic strategies and address challenges such as antimicrobial resistance and the need for better diagnostic tools.