Bioassays for the rapid detection and quantification of specific nucleic acids, proteins, and peptides are fundamental tools in many clinical settings. Traditional optical emission methods have focused on the use of molecular dyes as labels to track selective binding interactions and as probes that are sensitive to environmental changes. Such dyes can offer good detection limits based on brightness but typically have broad emission bands and suffer from time-dependent photobleaching. Inorganic nanoparticles such as quantum dots and upconversion nanoparticles are photostable over prolonged exposure to excitation radiation and tend to offer narrow emission bands, providing a greater opportunity for multiwavelength multiplexing. Importantly, in contrast to molecular dyes, nanoparticles offer substantial surface area and can serve as platforms to carry a large number of conjugated molecules. The surface chemistry of inorganic nanoparticles offers both challenges and opportunities for the control of solubility and functionality for selective molecular interactions by the assembly of coatings through coordination chemistry. This report reviews advances in the compositional design and methods of conjugation of inorganic quantum dots and upconversion nanoparticles and the assembly of combinations of nanoparticles to achieve energy exchange. Our interest is the exploration of configurations where the modified nanoparticles can be immobilized to solid substrates for the development of bioassays and biosensors that operate by resonance energy transfer (RET).