Surface plasmon resonance (SPR) sensors have been a mature technology for more than two decades now, however, recent investigations show continuous enhancement of their sensitivity and their lower detection limit. Together with the recent investigations in localized SPR phenomena, extraordinary optical transmission through nanoapertures in metals, and surface-enhanced spectroscopies, drastic developments are expected to revolutionize the field of optical biosensing. Sensitivity-enhancement (SE) techniques are reviewed focusing both on the physical transduction mechanisms and the system performance. In the majority of cases the SE is associated with the enhancement of the electromagnetic field overlap integral describing the interaction energy within the analyte. Other important mechanisms are the interaction between plasmons and excitons and between the analyte molecules and the metal surface. The lower detection limit can be reduced significantly if systems with high signal-to-noise ratio are used such as common-path interferometry, ellipsometry or polarimetry systems.