This article will review the most recent progress in the molecular diagnosis of sleeping sickness and its potential role in patient management and disease control. While PCR remains restricted to research and reference laboratories, promising alternative molecular platforms have emerged over the last few years. Several loop-mediated isothermal amplification assays have been developed for detection and identification of the parasite with reported high analytical sensitivity and specificity. Simplified loop-mediated isothermal amplification formats have been designed and are undergoing evaluation studies in the field. Accurate diagnosis based on specific detection of the parasite's ribosomal RNA has been made possible by the isothermal nucleic acid sequence-based amplification and by direct hybridization with fluorescent detection probes. In addition to the technological progress, the authors also discuss the diagnostic performance of molecular tests in the most recent clinical evaluation studies and briefly present some viewpoints for the near future.