This review focuses on (i) the current status of 1H NMR spectroscopy to quantify lipoprotein subclasses directly from serum or plasma, and (ii) the applications of 1H NMR metabonomics of serum in biomedicine. Related to both themes, experimental and data analysis methodologies are discussed together with the biochemical rationales. Particular emphasis is placed on the concepts of risk assessment and diagnostics in relation to the potential clinical role of 1H NMR metabonomics; recent applications in the area of coronary heart disease and diabetes are addressed in more detail.