PURPOSE OF REVIEW: Liquid biopsy analyses based on circulating cell-free nucleic acids, circulating tumor cells or other diseased cells from organs, and exosomes or other microvesicles in blood offer new means for non-invasive diagnostic applications. The main goal of this review is to explain the importance of preserving whole blood specimens after blood draw for use as liquid biopsies, and to summarize preservation solutions that are currently available. RECENT FINDINGS: Despite the great potential of liquid biopsies for diagnostics and disease management, besides non-invasive prenatal testing (NIPT), only a few liquid biopsy applications are fully implemented for routine in vitro diagnostic testing. One major barrier is the lack of standardized pre-analytical workflows, including the collection of consistent quality blood specimens and the generation of good-quality plasma samples therefrom. Broader use of liquid biopsies in clinical routine applications therefore requires improved pre-analytical procedures to enable high-quality specimens to obtain unbiased analyte profiles (DNA, RNA, proteins, etc.) as they are in the patient's body. SUMMARY: A growing number of stabilizing reagents and dedicated blood collection tubes are available for the post-collection preservation of circulating cell-free DNA (ccfDNA) profiles in whole blood. In contrast, solutions for the preservation of circulating tumor cells (CTC) that enable both, enumeration and molecular analyses are rare. Solutions for extracellular vesicle (EV) populations, including exosomes, do not yet exist.