More than 50 papers on surface plasmon resonance biosensors, published between 2016 and mid-2018, are reviewed. Papers concerning the determination of large particles such as vesicles, exosomes, cancer cells, living cells, stem cells, and microRNA are excluded, as these are covered by a very recent review. The reviewed papers are categorized into five groups, depending on the degree of maturity of the reported solution; ranging from simple marker detection to clinical application of a previously developed biosensor. Instrumental solutions and details of biosensor construction are analyzed, including the chips, receptors, and linkers used, as well as calibration strategies. Biosensors with a sandwich structure containing different nanoparticles are considered separately, as are SPR (Surface Plasmon Resonance) applications for investigating the interactions of biomolecules. An analysis is also made of the markers determined using the biosensors. In conclusion, there is shown to be a growing number of SPR applications in the solution of real clinical problems.