Improvement of transplantation strategies and a multitude of emerging novel therapies result in a better treatment outcome in patients with multiple myeloma (MM). This gives rise to the need for sensitive methods to detect minimal residual disease (MRD) in MM. Qualitative molecular monitoring using allele-specific oligonucleotide PCR for the immunoglobulin heavy chain (IgH) is well established to detect clonotypic cells after therapy or in stem cell harvests. Recently, real-time IgH PCR or limiting dilution based PCR assays offer the possibility to quantify the amount of residual tumour cells. In this review, different qualitative and quantitative IgH PCR techniques will be discussed as well as the current clinical role of molecular monitoring of MRD in patients with MM.