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This article presents a review of literature on effective teaching and learning  21st Century in Higher Order Thinking skills (HOTS) for science students  . It tries to explore what constitutes effective teaching in science.  The imperative in recent years about improving student outcomes is also about improving the quality of the teaching workforce.    However, recruiting and retaining quality teachers has become a challenge among some of countries. The teaching of Higher order Thinking  Skills (HOTS) has its own challenges and these challenges deserve due attention. In the 21st century, one critical aspect in discussing effective teaching and learning is examining the effectiveness of teachers in developing students’ capability to think while ensuring content mastery at the same time. As a matter of fulfilling a national aspiration in education, the role of teachers in inculcating HOTS is another important aspect of teaching HOTS effectively. There were at least 30 articles reviewed.   The related journal articles on factors effectiveness of teaching and learning  21st Century in Higher Order Thinking skills for science students were downloaded with cut off limit from 2001 to 2014. The articles were then analyzed and organized according to the definitions of  Higher Order Thinking skills and the  effectiveness  teaching and learning  21st Century. According to the literature reviewed, six   main domain of  affecting    teaching and learning of science of the 21st century in Higher Order Thinking Skills (HOTS)  could be identified. There were   : teachers quality , curriculum, assessment, students, environment and teaching aids. The paper discusses how these domain contribute to effective science teaching in science in detail. Finally, the importance of presenting research findings for reform attempts to improve the quality of teaching and learning in Malaysia schools is discussed.