This chapter focuses on two label-free technologies capable of measuring biomolecular interactions with high selectivity and sensitivity without the need for labels or secondary reagents. The identification of biomolecular interactions between peptides, proteins, nucleotides, DNA, cells, carbohydrates, small molecules, and other biomolecules plays a central role in the development of diagnostic tests and drug discovery studies. In many biosensor applications, biomolecules need to be immobilized on the quartz crystal surface in order to capture the target analyte, which obtains dynamic information relating to biomolecular interactions. Quartz crystal microbalance (QCM) and Surface Plasmon Resonance (SPR) are two very important label-free detection techniques that have been widely used in various applications, including biomedical research, chemical sensors, biosensors, food safety, and environmental monitoring. QCM and SPR are effective label-free detection techniques that have uses in numerous fields. Although QCR and SPR systems have different advantages over each other, QCM and SPR systems are very useful for detecting association properties.