CMOS sensors comprise an important tool in bioscientific applications. This review focuses on CMOS sensor-based molecular diagnostics of DNA, protein, and metabolic molecules. Herein, gene sequencing, DNA-DNA hybridization, single nucleotide polymorphisms (SNP), protein interactions, peptide interactions, antigen-antibody (Ag-Ab) interactions, as well as glucose and cholesterol monitoring using CMOS sensors are discussed along with existing experimental outcomes. CMOS sensor based electrochemical, optical, impedance, dual, continuous, and label-free analysis and their related integration techniques are explained. Moreover, we describe the utilization of a CMOS chip in microarray fabrication, assay platform development, and transducer incorporation for molecular diagnostics. Furthermore, CMOS sensor-based point-of-care (POC) applications, other biological analyses, and the role of nanoparticles in biomolecular sensing are discussed. Future directions include information about the novel integration of CMOS sensor-based molecular diagnostic devices with a central focus towards enhancement of POC approaches. This review is helpful in creating highly sensitive, cheaper, and user-friendly biomedical devices with modern dimensions. (C) 2015 Elsevier B.V. All rights reserved.