The quartz crystal microbalance-dissipation (QCM-D) is a simple, high-resolution and mass-sensing technique, based on the piezoelectric effect. Its importance rely in the ability to simultaneiously measure both the frequency and dissipation, where the former relates to mass and the later relates to viscoelasticity. The past decade has witnessed an explosive growth in the application of the QCM-D technique to the study of a wide range of molecular systems; protein, lipids, cells, DNA, enzymes, pathogens, biopolymer multi-layer build-up, in ng/cm2, to list a few. This review focuses on recent critical insights and applications in bionanoscience; mainly associated with conformational changes in nano-architecture of biomaterials and drug discovery. copyright © 2015 American Scientific Publishers.