Liquid biopsies represent an innovative methodology for cancer diagnostics and disease monitoring. The analysis of circulating cell-free nucleic acids (CFNA) and circulating tumour cells (CTC) are rapidly being adopted for quantitative and qualitative characterisation of the tumour genome and as a mode of non-invasive therapeutic monitoring. Circulating cell-free DNA (cfDNA) and CTC are representative of the underlying mutational profile of a cancer whereas the evaluation of extracellular RNA (exRNA) can be utilised as a prognostic biomarker thus providing critical biological information both at the time of diagnosis and during disease evolution. In this chapter, we will review the emerging utility of CFNA and CTC as biomarkers of prognosis and for both mutational characterisation and monitoring disease progression, and how these have the potential to provide additional information as an adjunct to bone marrow biopsies and conventional disease markers in multiple myeloma (MM). Emerging data suggest that liquid biopsies might offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognostication and therapeutic decision making in MM, with particular applicability in subsets of patients where conventional markers of disease burden may be less informative.