Small and Medium Enterprises (SMEs) face new challenges in the global market as customers require more complete and flexible solutions and continue to drastically reduce the number of suppliers. SMEs are trying to address these challenges through cooperation within collaborative enterprise networks (CENs). Human aspects constitute a fundamental issue in these networks as people, as opposed to organizations or Information Technology (IT) systems, cooperate. Since there is a lack of empirical studies on the role of human factors in IT-supported collaborative enterprise networks, this paper addresses the major human aspects encountered in this type of organization. These human aspects include trust issues, knowledge and know-how sharing, coordination and planning activities, and communication and mutual understanding, as well as their influence on the business processes of CENs supported by IT tools. This paper empirically proves that these aspects constitute key factors for the success or the failure of CENs. Two case studies performed on two different CENs in Switzerland are presented and the roles of human factors are identified with respect to the IT support systems. Results show that specific human factors, namely trust and communication and mutual understanding have to be well addressed in order to design and develop adequate software solutions for CENs.