Semiconductor quantum dots (QDs) exhibit unique optical and photophysical properties. These features are implemented to develop optical molecular sensor systems. The review addresses the methods to functionalize the QDs with chemical capping layers that enable the use of the resulting hybrid structures for sensing, and discusses the photophysical mechanisms being applied in the different sensor systems. Different methods to design the chemically-modified QDs hybrid structures for sensing low-molecular-weight substrates, metal ions, anions and gases are presented. These include the functionalization of the QDs with ligands that bind ions, the modification of the QDs with substrate-specific ligands or receptor units, and the chemical modification of the QDs upon sensing. Specific emphasis is directed to describe the cooperative catalytic functions of the QDs in the sensing processes, and to address the function of sensing with logic-gate operations.