BACKGROUND: The current methodology used to detect, diagnose, and monitor many types of cancers requires invasive tissue biopsy testing. Recently, liquid biopsy using blood, plasma, urine, saliva, and various other bodily fluids has shown utility to solve many issues associated with tissue biopsy. Blood/plasma has received most of the attention within the liquid biopsy field, however, obtaining blood samples from patients is still somewhat invasive and requires trained professionals. Using urine to detect cell-free DNA cancer biomarkers offers a truly non-invasive sampling method that can be easily and reproducibly conducted by patients. CONTENT: Novel technologies and approaches have made the detection of small quantities of cell-free tumor DNA of varying lengths possible. Recent studies using urine circulating tumor DNA to detect cancer mutations and other biomarkers have shown sensitivity comparable to blood/plasma cell-free DNA liquid biopsy for many cancer types. Thus, urine cell-free DNA liquid biopsy may replace or provide supplementary information to tissue/blood biopsies. Further investigation with larger patient cohorts and standardization of pre-analytical factors is necessary to determine the utility of urine cell-free DNA liquid biopsy for cancer detection, diagnosis, and monitoring in a clinical setting. SUMMARY: In this mini-review we discuss the biological aspects of cell-free DNA in urine, numerous studies using urine cell-free DNA to detect urological cancers, and recent studies using urine cell-free DNA to detect and monitor non-urological cancers including lung, breast, colorectal, and other cancers.