In the overall planning of a manned mission to Mars, all the issues related to human involvement are critical. To a certain extent, they dictate the most severe constraints on the mission scenario and spacecraft architecture.Despite this unanimously recognized importance, limited efforts have been devoted up to now to dedicated research activities on human-related aspects, partially neglected w.r.t. more technical areas like orbital dynamics, propulsion, power generation, etc.This paper summarizes the major results of a survey on the human factors of long duration missions performed by Alenia Spazio in the frame of an ESA study, MARSEMSI, whose aim was to identify possible scenarios and related infrastructure requirements for a manned mission to Mars.The many relevant topics addressed to obtain a global understanding of this field have been organized in three main groups: Physiopathological aspects, involving crew health and performance, specifically analyzed in a Mars manned mission on the crew well-being perspective. The effects of the space natural environments on the crew well-being as well as those due to the spacecraft and mission operation environments are considered here. Specific aspects of Health Maintenance are addressed as they might occur during such a long-duration mission. Human interaction related aspects, including the complex of psychological problems arising from crew interaction during the mission in the frame of their artificial society. An effective crew selection and training process and a suitable crew support during the mission are regarded as fundamental factors for the overall mission success. Man-system integration aspects have also to be carefully considered from the very beginning of the Mars mission planning, as the mutual interrelationship between man and machine is critical for mission safety and success. Issues such as habitability, life support, man-machine integration and task sharing optimization are examined. Finally, considerations regarding the criticality of all the identified aspects are presented, with the aim of highlighting those requiring a more in-depth research effort in the years to come, and with the clear baseline that the complex network of links between man, system and environment is the variable to be optimized.