A high-performance cleanroom should provide efficient energy performance in addition to effective contamination control. Energy-efficient designs can yield capital and operational cost savings, and can be part of a strategy to improve productivity in the cleanroom industry. Based upon in-situ measurement data from ISO Class 5 clean rooms, this article discusses key factors affecting cleanroom air system performance and benefits of efficient airflow design in clean rooms. Cleanroom HVAC systems used in the semiconductor, pharmaceutical, and healthcare industries are very energy intensive, requiring large volumes of cleaned air to remove or dilute contaminants for satisfactory operations. There is a tendency, however, to design excessive airflow rates into cleanroom HVAC systems, due to factors such as design conservatism, lack of thorough understanding of airflow requirements, concerns about cleanliness reliability, and potential design and operational liabilities. Energy use of cleanroom environmental systems varies with system type and design, cleanroom functions, and the control of critical parameters such as temperature and humidity. In particular, cleanroom cleanliness requirements specified by cleanliness class have an impact on overall energy use. A previous study covering Europe and the US reveals annual cleanroom electricity usage for cooling and fan energy varies significantly depending on cleanliness class, and may account for up to three-quarters of total annual operating costs. A study on a semiconductor cleanroom in Japan found air delivery systems account for more than 30% of total power consumption. It is evident that the main factors dictating cleanroom operation energy include airflow rates and HVAC system efficiency. Improving energy efficiency in clean rooms may potentially contribute to significant savings in the initial costs of the facilities as well as operation and maintenance costs. For example, energy consumption by a typical chip manufacturer can be cut 40% or more, and the associated greenhouse emissions even more. Cleanroom HVAC systems provide huge opportunities for energy savings in the semiconductor industry. In addition to direct cost reductions in cleanroom investment and operation, energy-efficient designs can reduce maintenance costs, increase power reliability, improve time-to-market in cleanroom production, and improve environmental quality. Companies that use energy efficiency to lower costs and increase productivity can gain a competitive advantage and achieve a higher return on investment. In addition, energy-efficient cleanroom systems conserve energy and natural resources, heightening the company's reputation as an environmentally conscious leader in the community and the industry. A significant portion of energy use in cleanroom environmental systems is associated with recirculating air systems. We will review and analyze design factors and operational performance of airflow systems in ISO Class 5 clean rooms. We will also discuss benefits of efficient cleanroom airflow designs in conjunction with effective cleanroom contamination control. We will consider the following common recirculating air system designs: fan-tower (FT) with pressurized-plenum; distributed air handler unit (AHU); and fan-filter unit (FFU).