The article deals with some issues of psychophysiological support (PPS) of manned space flights discussed with Academician O.G. Gazenko. It has been shown that even at the initial stages of development of space flights (SFs), monitoring and evaluation of the mental state and working capacity of crew members were regarded as the key components of PPS and merited special comprehensive studies with the development of associated methods. The polyeffectors method for recording physiological functions, such as electrocardiogram, electroencephalogram, and skin-galvanic reaction, was recognized as a potent tool in gathering information for the assessment of the current state of health. In the period of the performance of long-term orbital flights, starting with the 96-day flight of Yu. Romanenko and G. Grechko, the system of psychological support developed at the Institute for Biomedical Problems (IBMP), under the leadership of Gazenko was introduced into PPS, and then used in all flights of the stations Salyut and Mir, and now at the International Space Station. Evidently, the use of this system made a significant contribution to the PPS and maintenance of health and working efficiency of crews.