Humidity control is pivotal to maintain occupant thermal comfort and suppress mold growth in indoor environments. Furthermore, poor indoor air quality (IAQ) due to the presence of volatile organic compounds (VOCs) and high concentrations (>1,000 ppm) of CO2 can cause health issues and negatively affect cognitive performance. Therefore, providing high-quality indoor air has gained significant attention over the past decade. Conventional cooling coil and filter-based HVAC systems have limited capability to meet the augmented demand for occupant thermal comfort and high indoor air quality. Moreover, modern buildings are increasingly airtight to save energy, and increasing ventilation to mitigate VOC and CO2 concentration is discouraged. Separate sensible and latent cooling technology using a rotary desiccant wheel presents a promising solution in this respect. Because of the development of desiccant materials with high water vapor, VOC, and CO2 uptake, desiccant wheels can be used as an integrated technology option for IAQ management. To promote desiccant wheel use for energy-efficient management of IAQ in buildings, this article reviews recent advancements in using desiccant wheels for dehumidification, VOC mitigation, and CO2 capture from outdoor air. Finally, the article presents the authors' perspective by summarizing the key research gaps in the field and discussing the future direction of research to address these gaps from two different aspects, namely, suitable adsorbent material development and desiccant wheel design.