Bilirubin is a yellow tetrapyrrole molecule found in the gastrointestinal system, and it is produced when hemoglobin (Hb) is degraded. For treating various liver disorders like jaundice, serum bilirubin in the body is a testing marker. Jaundice develops when the serum bilirubin level is more significant than 2.0 to 2.5 mg/dl. Examining different forms of bilirubin, i.e., conjugated (direct) bilirubin, unconjugated (indirect) bilirubin, and total bilirubin, helps the physician identify the cause and metabolic disorder of jaundice. Inconsistent bilirubin production and removal results in lasting neurologic consequences (kernicterus). In this paper, we have presented a brief introduction to jaundice, the physiological mechanism of bilirubin, its types and causes, clinical approaches toward patients having jaundice, i.e., the conventional method being practiced in clinical laboratories, and various non-invasive systems in the point-of-care settings along with their advantages and disadvantages. Information on bilirubin production and elimination with tracking of bilirubin levels may help to guide the proper clinical management of jaundice. The primary focus is on the progression of established methodologies and techniques to newer ones capable of measuring bilirubin in biological materials.