Despite efforts to incorporate inquiry-based instruction into various science curricular, its adoption has been slow-paced. This has raised many concerns about challenges in the enactment of inquiry-based instruction. Therefore, this article seeks to provide an understanding of the challenges by exploring the perspectives of teachers in the research literature, as well as suggest possible ways of coping with these challenges. The review of literature has indicated that the identification of what constitutes appropriate guidance in inquiry-based instruction, the threat of time management, teachers’ deficiency in inquiry instructional techniques and strategies constitute the most challenges. Although there are strong criticisms against guided inquiry instruction, this study has found that it represents the most appropriate guidance for optimal science learning. A sustained all-year-round training program with support from teaching colleagues and from administration may certainly impact teachers’ self-efficacy in inquiry instruction. With the level of progress made in inquiry instruction research, and the pace of advancement of technology, the future of the adoption and enactment of inquiry in the classroom can only be brighter. Future research needs to focus on determining the effects of a more sustained all-year-round professional development model on the level of teachers’ achievement in inquiry-based instruction.