Nephrolithiasis is the most common health condition affecting the kidney and urinary tract and constitutes a major global health-care problem. The prevalence of nephrolithiasis has increased substantially over the past five decades, irrespective of age, sex or ethnicity. Kidney stones cause substantial morbidity, reduced quality of life and enormous health-care expenditure, largely due to their frequent recurrence. Furthermore, nephrolithiasis is now recognized as a systemic condition associated with increased risks of chronic kidney disease, cardiovascular disease, metabolic syndrome and low bone mass. Nephrolithiasis exhibits marked pathophysiological heterogeneity. Dietary and environmental exposures interact with genetic predisposition to shape individual disease risk. Calcium oxalate stones are most prevalent, commonly driven by hypercalciuria, hyperoxaluria, hypocitraturia and low urine volume, whereas the formation of uric acid and calcium phosphate stones is commonly linked to urinary pH. A comprehensive clinical evaluation can uncover underlying metabolic abnormalities, distinguish idiopathic, secondary and Mendelian forms of nephrolithiasis, identify systemic disease associations and guide therapy. Recurrence prevention requires individualized strategies that combine dietary and pharmacological interventions. For established stones, surgical management is effective, with ureteroscopy and percutaneous nephrolithotomy achieving high stone-free rates. Despite its considerable clinical and societal burden, nephrolithiasis remains under-recognized, underserved and under-researched. Greater awareness and investments in research, innovation and education are urgently needed.