Mental performance of astronauts during spaceflight may suffer from both direct effects of microgravity on perceptual, cognitive, and psychomotor processes, and unspecific stress effects on these functions due to high workload sleep disturbances, or the general burden of adapting to the extreme living conditions in space. Early detection of any signs of mental performance impairments seems to be essential for mission success and to prevent obvious performance decrements in critical mission tasks. One possible approach to this problem is to assess the astronaut's performance on specific screening tests repeatedly during a space mission and to compare the results with a self-referenced baseline established pre-flight. The selection of screening tests for this purpose should be guided by three different criteria: 1) their reliability; 2) their sensitivity (i.e., their power to reveal subtle mental performance changes induced by internal or external stressors during spaceflight); and 3) their diagnosticity (i.e., their capability to reveal the underlying processes that lead to these performance deficits). Based on a discussion of these theoretical issues, first attempts to monitor mental performance of astronauts during spaceflight by means of short-term laboratory tasks are reviewed. The results of these studies suggest that, in particular, perceptual-motor tasks (tracking) and tasks placing comparatively high demands on attentional processes (e.g., dual-tasks) represent sensitive monitoring measures. First studies on the diagnositicity of tracking performance decrements during spaceflight suggest that they reflect both microgravity-related changes in the sensory-motor system as well as unspecific stress-effects, with the former factor reflected primarily in tracking performance decrements during early adaptation to the microgravity environment.