Reliability is a primary concern for designers and operators of life support systems. Measuring the reliability of advanced life support systems that use biological processes for regeneration presents a unique challenge to reliability engineers. The challenge lies in trying to define the reliability of a biological component (e.g., a green plant) and combine that with the reliability of physical components (e.g., a pump) to obtain a total system reliability. This paper presents issues to consider while trying to determine and to predict the reliability of such systems. The physiological response of a plant to its environment can be compared to the response of a physical component to its operating environment, and a measure of reliability can be determined. Furthermore, the physiological response of a plant can be estimated for most environmental conditions, and this estimation is necessary for the prediction of total system reliability.