Relapse represents the main cause of treatment failure after stem cell transplantation (SCT). Thus, monitoring of minimal residual disease (MRD) in allografted patients allows an early detection of recurrence and a subsequent intervention prior to clinically detectable relapse. MRD assessment by polymerase chain reaction-based methods is currently part of the routine clinical management of patients with chronic myeloid leukemia after allo-SCT. It is also recognized that it is a useful prognostic tool in several mature lymphoid and plasma cell disorders such as chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma, and multiple myeloma. In some of these entities, clinical trials employing MRD as a decision-making tool are currently ongoing and will define whether sensitive MRD detection allows for earlier therapeutic intervention to improve the outcome of SCT. We here discuss the methods of MRD evaluation in lymphoid and plasma cell disorders following transplantation with the ultimate aim of providing critical information for the setup of molecular approaches to detect MRD.