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Background: Repeated exposure to heat (ie, plasma volume expansion) or altitude (ie, increase in total hemoglobin mass), in conjunction with exercise, induces hematological adaptations that enhance endurance performance in each respective environment. Recently, combining heat and altitude training has become increasingly common for athletes preparing to compete in temperate, sea-level conditions. Purpose: To review the physiological adaptations to training interventions combining thermal and hypoxic stimuli and summarize the implications for temperate, sea-level performance. Current Evidence: To date, research on combining heat and hypoxia has employed 2 main approaches: simultaneously combining the stressors during training or concurrently training in the heat and sleeping at altitude, sometimes with additional training in hypoxia. When environmental stimuli are combined in a training session, improvements in aerobic fitness and time-trial performance in temperate, sea-level conditions are generally similar in magnitude to those observed with heat, or altitude, training alone. Similarly, training in the heat and sleeping at altitude does not appear to provide any additional hematological or nonhematological benefits for temperate; sea-level performance relative to training in hot, hypoxic, or control conditions. Conclusions: Current research regarding combined heat and altitude interventions does not seem to indicate that it enhances temperate, sea-level performance to a greater extent than “traditional” (heat or hypoxia alone) training approaches. A major challenge in implementing combined-stressor approaches lies in the uncertainty surrounding the prescription of dosing regimens (ie, exercise and environmental stress). The potential benefits of conducting heat and altitude exposure sequentially (ie, one after the other) warrants further investigation.