Albuminuria—increased urine albumin excretion—is associated with cardiovascular mortality among patients with diabetes, hypertension, chronic kidney disease, or heart failure, as well as among adults with few cardiovascular risk factors. Many authors have hypothesized that albuminuria reflects widespread endothelial dysfunction, but additional work is needed to uncover whether albuminuria is directly pathologic or causative of cardiovascular disease. Urinary albumin-to-creatinine ratio is an attractive, unifying biomarker of cardiovascular, kidney, and metabolic conditions that may be useful for identifying and monitoring disease trajectory. However, albuminuria may develop through unique mechanisms across these distinct clinical phenotypes. This state-of-the-art review discusses the role of albuminuria in cardiovascular, kidney, and metabolic conditions; identifies potential pathways linking albuminuria to adverse outcomes; and provides practical approaches to screening and managing albuminuria for clinical cardiologists. Future research is needed to determine how broadly and how frequently to screen patients for albuminuria, whether it is cost-effective to treat low-grade albuminuria (10–30 mg/g), and how to equitably offer newer antiproteinuric therapies across the spectrum of cardiovascular-kidney-metabolic diseases.