This study explores e-portfolio practices among K-12 teachers and investigates their perceptions, attitudes and skills towards the potentials of e-portfolios to enhance the required 21st century competencies. Both qualitative and quantitative methods were used to investigate teachers' perceptions of the use of e-portfolios in both public and private sectors in the seven Emirates of the UAE. In addition, 10 school leaders were interviewed to explore how willing and able they were in supporting a hypothetical change in the practice of documentation by using e-portfolios. A survey was conducted with over 400 teachers responding to 54 questions via an online questionnaire supported by the Survey Monkey web service tool. Data analysis results revealed that a substantial proportion of participants felt positively towards the possibility of using e-portfolios. However, the survey also revealed that the majority of teachers in the field need to acquire knowledge, associated skills, and competencies, through professional developmental training programs to cultivate and improve reflective, selective, organizational, constructive feedback skills, along with familiarity and proficiency in using online collaborative and professional networking tools. The study concludes with implications for policy-makers and stakeholders to consider before introducing requirements and regulations on e-portfolios.